Medical Biotechnology Research Papers - Academia.edu (original) (raw)

2025, Circulation. Cardiovascular genetics

Background -The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multi-ethnic genome-wide association studies. We included 21,079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (N=17,936), African (N=1,943), Hispanic (N=795), and Asian (N=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each SNP and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (p=2.7x10 -19 ) and identified novel loci on chr10q24 (p=1.6x10 -9 ) and chr2p21 (p=4.4x10 -8 ). In the multi-ethnic meta-analysis, we identified two additional loci, on chr1q22 (p=2.0x10 -8 ) and chr2p16 (p=1.5x10 -8 ). The novel loci contained genes that have been implicated in Alzheimer's disease (chr2p21, chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24, chr2p16). Conclusions -We identified four novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of white matter hyperintensities in addition to previously-proposed ischemic mechanisms.

2025, Anais do IV International Symposium on Immunobiological e VII Seminário Anual Científico e Tecnológico de Bio-Manguinhos

In Brazil, the improvements in sanitary conditions and the recent inclusion of hepatitis A vaccine resulted in an increase in the number of individuals susceptible to the disease. These facts together with the circulation of the virus in the environment, increases the occurrence of epidemic outbreaks. Therefore, a test that enables a rapid and large-scale diagnosis of acute cases may be a promising alternative to the currently available immunoenzymatic assays. In this way, Biosensor assay may help in the adoption of appropriate measures to contain hepatitis A outbreaks, as well as, in the detection of susceptible individuals involved in the outbreak that may be candidates for vaccination, avoiding the spread of the infection Objective: The objective of this study was to standardize an immunosensor of reflectance applied to the large-scale immunodiagnosis of hepatitis A. This methodology was based on the development of a reflectance biosensor for the detection of IgM and IgG anti-HAV, which allows the detection of antibodies at low detection limits (nanoscale) and monitor the antigen-antibody reactions in real time, without the use of conjugated developers and, with high selectivity and low cost. For detection of anti-HAV IgM and IgG antibodies, the chip sensor surface was adsorbed with different concentrations of recombinant HAV VP1 protein (0.001 μg -0.5 μg) in run buffer. Purified anti-HAV IgM and IgG in different concentrations (3.5nM to 219pM) were applied in triplicate, to evaluate the interaction of anti-HAV antibodies with HAV VP1 and the limit of detection of the assay. After the step of interacting the specific antibodies with the VP1 protein and recording the data in a sensorgram, the surface of the sensor chip was regenerated, so that a second interaction with antibodies could occur. A panel of anti-HAV IgG and IgM reactive and non-reactive serum samples were used to evaluate the sensitivity, specificity and reproducibility of this assay. Results: Purified anti-HAV IgM and IgG were detected in different concentrations (0.02µg to 0.17µg). The increase in the detection signal was proportional to the increase in anti-HAV concentrations. It was possible to define the binding affinity (1.85nM and 1.20nM) and the maximum response (86,42 RU and 90,33 RU) to IgM and IgG, respectively. The linearization of the antibodies concentration curves generated a saturation constant, which allowed inferring the amount of specific antibodies in the anti-HAV positive serum compared to the negative serum. Through the panel of serum samples, it was observed that the detection signal of the anti-HAV positive serum samples was three times greater than the signal of the negative serum samples. These preliminary results demonstrated that the biosensor was able to identify with high sensitivity, the presence of specific anti-HAV antibodies in sera of patients.

2025, Materials

In this study, femtosecond laser-induced sub-micrometer structures are generated to modify polyethylene (PE) surface topographies. These surfaces were subjected to bacterial colonization studies with Escherichia coli and Staphylococcus aureus as test strains. The results reveal that the nanostructures do not influence S. aureus coverage, while the adhesion of E. coli is reduced.

2025, Journal of Nanoanalysis

Although ZnO nanoparticles possess novel properties that make them available to a wide range of applications, the questions regarding their safety may arise when they come in direct contact with biological systems (such as skin, lungs, and tissues). In this study, we evaluated the possible toxic effects of different dosages of zinc oxide nanoparticles (25, 50 and 100 mg/kg) in three treatment groups in four weeks on skin and muscle tissues of treated rats. For toxicological assessments, male rats weighing 150 to 200 g were exposed to three different concentrations of zinc oxide nanoparticles (25, 50 and 100mg/kg) in an acute study. Toxic responses were assessed by clinical and histopathologic parameters. In all experimental animals the sites of exposure were scored for any type of dermal toxicity and compared with the negative control group. All changes were compared with the negative control group and the results were analyzed by one-way analysis of variance (ANOVA). Results have been indicated that the mean levels of the histopatological injuries were scored in experimental groups and showed no significant difference with control group that mean,the number of vacuole degeneration showed significant increase in high dose group (p<0.05). The results showed that the topical application of zinc oxide cannot make remarkable effects on the skin and skeletal muscle tissue of the rats in low and medium doses. Although, we did not find any harmful effects on the use of low and medium dosages of zinc oxide nanoparticles on the skin and musculoskeletal system, we cannot ignore the observations regarding the sensitivity of cells and tissues to the potential cytotoxic effects this kind of nanoparticles. Therefore, it is suggested to conduct further researches on the complex toxicity mechanism of zinc oxide nanoparticles in living organisms.

2025, Impact of Antibacterial Agents in Horticulture: Risks to Non-Target Organisms and Sustainable Alternatives

The global population is rising at an alarming rate and is projected to reach 10 billion by 2050, necessitating a substantial increase in food production. However, the overuse of chemical pesticides, including antibacterial agents and synthetic fertilizers, poses a major threat to sustainable agriculture. This review examines the ecological and health impacts of antibacterial agents (e.g., streptomycin, oxytetracycline, etc.) in horticultural crops, focusing on their effects on non-target organisms such as beneficial microbes involved in plant growth promotion and resistance development. Certain agents (e.g., triclosan, sulfonamides, and fluoroquinolones) leach into water systems, degrading water quality, while others leave toxic residues in crops, leading to human health risks like dysbiosis and antibiotic resistance. To mitigate these hazards, sustainable alternatives such as integrated plant disease management (IPDM) and biotechnological solutions are essential. Advances in genetic engineering including resistance-conferring genes like EFR1/EFR2 (Arabidopsis), Bs2 (pepper), and Pto (tomato) help combat pathogens such as Ralstonia solanacearum and Xanthomonas campestris. Additionally, CRISPR-Cas9 enables precise genome editing to enhance inherent disease resistance in crops. Emerging strategies like biological control, plant-growth-promoting rhizobacteria (PGPRs), and nanotechnology further reduce dependency on chemical antibacterial agents. This review highlights the urgent need for sustainable disease management to safeguard ecosystem and human health while ensuring food security.

2025, Nutrition Today

Personalized wellness encompasses individualized diet treatment plans, exercise regimens, and antistress programs. In time, it will include health and nutrition recommendations and programs based almost solely on one’s genetic profile and predispositions. But how evolved is the science behind these products and services and where do the greatest opportunities lie to improve public health? This article reviews the state of the science and technologies and products currently driving the personalized wellness marketplace. It considers how highly developed genomics science is and whether the field is truly at the point of creating diet and fitness plans for individuals based on their genetic profiles. It is intended to explore how the science and technology may coevolve in the future.

2025, Nanomedicine

Aims: The addition of carbon nanotubes (CNTs) remarkably improves the mechanical characteristics of base materials. CNT/alumina ceramic composites are expected to be highly functional biomaterials useful in a variety of medical fields. Biocompatibility and bone tissue compatibility were studied for the application of CNT/alumina composites as biomaterials. Methods & results: Inflammation reactions in response to the composite were as mild as those of alumina ceramic alone in a subcutaneous implantation study. In bone implantation testing, the composite showed good bone tissue compatibility and connected directly to new bone. An in vitro cell attachment test was performed for osteoblasts, chondrocytes, fibroblasts and smooth muscle cells, and CNT/alumina composite showed cell attachment similar to that of alumina ceramic. Discussion & conclusion: Owing to proven good biocompatibility and bone tissue compatibility, the application of CNT/alumina composites as biomaterials that contact...

2025, Agronomy

A plant tissue culture protocol from stevia was optimized for the production of planting materials and the natural sweetener, rebaudioside A. The highest survivability (88.90% ± 5.55) of explants was achieved at 15 and 30 days after culture initiation (DACI) on Murashige and Skoog (MS) media by sterilization with 30% Clorox (5 min) and 10% Clorox (10 min), respectively. Supplementation of MS with 0.50 mg/L 2,4-Dichlorophenoxyacetic acid (2,4-D) and 0.10 mg/L zeatin produced 50% callus at 15 DACI while 1.50 mg/L 2,4-D and 0.10 mg/L zeatin at 30 DACI increased callus production to 76.67%. The highest shoot proliferation per callus was achieved with 10.00 mg/L 6-benzyl amino purine (BAP) in MS at 15 DACI (5.80) and 30 DACI (12.33). The longest shoots of 4.31 cm and 6.04 cm at 15 and 30 DACI, respectively, were produced using BAP (10.00 mg/L) and 1.00 mg/L naphthalene acetic acid (NAA). MS media (0.50 strength) induced 2.86 and 6.20 roots per shoot and produced 3.25 cm and 7.82 cm long ...

2025, Nanomedicine (London, England)

To date, guidance on how to incorporate in vitro assays into integrated approaches for testing and assessment of nanomaterials is unavailable. In addressing this shortage, this review compares data from in vitro studies to results from in vivo inhalation or intratracheal instillation studies. Globular nanomaterials (ion-shedding silver and zinc oxide, poorly soluble titanium dioxide and cerium dioxide, and partly soluble amorphous silicon dioxide) and nanomaterials with higher aspect ratios (multiwalled carbon nanotubes) were assessed focusing on the Organisation for Economic Co-Operation and Development (OECD) reference nanomaterials for these substances. If in vitro assays are performed with dosages that reflect effective in vivo dosages, the mechanisms of nanomaterial toxicity can be assessed. In early tiers of integrated approaches for testing and assessment, knowledge on mechanisms of toxicity serves to group nanomaterials thereby reducing the need for animal testing.

2025, Molecules

Glioblastoma is an aggressive cancer, against which medical professionals are still quite helpless, due to its resistance to current treatments. Scorpion toxins have been proposed as a promising alternative for the development of effective targeted glioblastoma therapy and diagnostic. However, the exploitation of the long peptides could present disadvantages. In this work, we identified and synthetized AaTs-1, the first tetrapeptide from Androctonus australis scorpion venom (Aa), which exhibited an antiproliferative effect specifically against human glioblastoma cells. Both the native and synthetic AaTs-1 were endowed with the same inhibiting effect on the proliferation of U87 cells with an IC50 of 0.56 mM. Interestingly, AaTs-1 was about two times more active than the anti-glioblastoma conventional chemotherapeutic drug, temozolomide (TMZ), and enhanced its efficacy on U87 cells. AaTs-1 showed a significant similarity with the synthetic peptide WKYMVm, an agonist of a G-coupled for...

2025, Texila International Journal of Public Health

Customizing treatments according to each patient's distinct genetic, molecular, and clinical traits, precision medicine holds the potential to completely transform the way cancer is treated. Advances in immunotherapy, liquid biopsy technology, multi-omics, and gene editing methods like CRISPR are all contributing to this strategy. By combining these advancements, it will be possible to develop tailored medicines that focus on the underlying genetic causes of cancer, increasing the precision and efficacy of cancer treatments. Furthermore, machine learning and artificial intelligence provide strong instruments for forecasting therapy outcomes and refining therapeutic approaches. Widespread adoption is still hampered by issues like the intricacy of cancer genetics, the high expense of sophisticated therapies, restricted access in environments with limited resources, and the requirement for uniform clinical data. In order to alter global cancer treatment and improve patient outcomes, it will be imperative to address these issues and guarantee that all patients may benefit from precision medicine.

2025, Clinical & Experimental Pharmacology

Objective: In Indian traditional medicine, decoctions from different parts of Stereospermum suavelolens are used for the treatment of various human diseases including diabetes mellitus. The present study was aimed to evaluate ethyl acetate fraction of ethanol extract from Stereospermum suavelolens for nephroprotective effects in Streptozotocin (STZ)-induced diabetic rats by sub acute model. The STZ induced diabetic rats were treated once daily, orally with ethyl acetate fraction of Stereospermum suavelolens for 14 days at the doses of 200 and 400 mg/kg. The serum and urine renal function parameters-creatinine, urea, uric acid, albumin and total proteins were measured on 15 th day. The in vivo antioxidant activity of Stereospermum suavelolens was also evaluated in diabetic rats. Effects of the fraction treatments on the kidney histological profile in STZ nephrotoxic rats were also evaluated. The present study investigation showed that the ethyl acetate fraction of Stereospermum suavelolens significantly (P<0.001) attenuated elevations in the serum levels of creatinine, urea, uric acid and total proteins in diabetic treated rats as compared with diabetic control rats. Significant (P<0.001) increase in Superoxide Dismutase (SOD), reduced Glutathione (GSH) and Catalase (CAT) levels and reduction in Thiobarbituric Acid Reactive Substances (TBARS) levels were also observed in ethyl acetate fraction treated rats kidney. The histopathological study of kidney in drug treated rats shows significant protective effect against STZ oxidative stress. Our study concludes that the ethyl acetate fractions of Stereospermum suavelolens possess potent nephroprotective effect against oxidative stress in STZ induced diabetic rats.

2025, Cellular Physiology and Biochemistry

Rod outer segment membrane guanylate cyclase (ROS-GC1) is a bimodal Ca 2+ signal transduction switch. Lowering [Ca 2+ ] i from 200 to 20 nM progressively turns it "ON" as does raising [Ca 2+ ] i from 500 to 5000 nM. The mode operating at lower [Ca 2+ ] i plays a vital role in phototransduction in both rods and cones. The physiological function of the mode operating at elevated [Ca 2+ ] i is not known. Through comprehensive studies on mice involving gene deletions, biochemistry, immunohistochemistry, electroretinograms and single cell recordings, the present study demonstrates that the Ca 2+ -sensor S100B coexists with and is physiologically linked to ROS-GC1 in cones but not in rods. It up-regulates ROS-GC1 activity with a K 1/2 for Ca 2+ greater than 500 nM and modulates the transmission of neural signals to cone ON-bipolar cells. Furthermore, a possibility is raised that under pathological conditions where [Ca 2+ ] i levels rise to and perhaps even enter the micromolar range, the S100B signaling switch will be turned "ON" causing an explosive production of CNG channel opening and further rise in [Ca 2+ ] i in cone outer segments. The findings define a new conespecific Ca 2+ -dependent feature of photoreceptors and expand our understanding of the operational principles of phototransduction machinery.

2025, Journal of advanced Biomedical and Pharmaceutical Sciences

Gene therapy is the “products that mediate their effects by transcription and/or translation of transferred genetic material and/or by integrating into the host genome and that are administered as nucleic acids, viruses, or genetically engineered microorganisms. The products may be used to modify cells in-vivo or transferred to cells ex-vivo prior to administration to the recipient”. Generally, gene therapies must retain two main criteria: (a) they contain an active material consists of nucleic acids such as deoxyribonucleic acid (DNA) or small interfering ribonucleic acid (siRNA). These macro molecules have the ability to regulate, repair, replace, add, or delete a genetic sequence; (b) the therapeutic, prophylactic, or diagnostic effect of these molecules are related directly to its gene sequence they contain or to the product of gene expression of this sequence. Gene therapies are directed mainly to treat multiple incurables, debilitating, and genetic diseases which have never tr...

2025, Nanomedicine (London, England)

2025

Anorexia nervosa (AN) is a condition in which an individual possess low body weight, obsession with having a thin figure, fear of gaining weight and inappropriate eating habit. It is often coupled with a distorted self-image. Irrational fear of gaining weight and immoderate eating habits may cause it. People suffering from anorexia nervosa have low leptin level and high tryptophan levels. Tryptophan and zinc levels have their eminent effect on anorexia nervosa. Tryptophan synthesizes serotonin, in brain neurons and stored in vesicles. Serotonin (5 hydroxy-tryptophan--5-HT) is a neurotransmitter in the brain that has an enormous influence over many brain functions, involving appetite control. Zinc is involved in numerous aspects of cellular metabolism. Zinc daily intake is required to maintain a steady state as no specialized zinc storage system has found in body. Tryptophan and zinc serum levels were determined in 40 subjects out of which 20 were suffering from anorexia nervosa and ...

2025, European Journal of Cancer and Clinical Oncology

2025, Deep Science Publishing

2025, BioMed Research International

The pronounced effect of extracellular matrix (ECM) scaffolds in supporting tissue regeneration is related mainly to their maintained 3D structure and their bioactive components. These decellularized matrix scaffolds could be revitalized before grafting via adding stem cells, fibroblasts, or keratinocytes to promote wound healing. We reviewed the online published literature in the last five years for the studies that performed ECM revitalization and discussed the results of these studies and the related literature. Eighteen articles met the search criteria. Twelve studies included adding cells to acellular dermal matrix (ADM), 3 studies were on small intestinal mucosa (SIS), one study was on urinary bladder matrix (UBM), one study was on amniotic membrane, and one study included both SIS and ADM loaded constructs. We believe that, in chronic and difficult-to-heal wounds, revitalizing the ECM scaffolds would be beneficial to overcome the defective host tissue interaction. This belief...

2025, Biomedical materials (Bristol, England)

Due to the numerous biological applications of Magnetite [Fe3O4] nanoparticles (MNPs), it is essential to identify the influence of these nanoparticles on basic biological processes. Therefore, in this research, the effect of MNPs on the structure and activity of hen egg white lysozyme (HEWL) (EC 3.2.1.1) as a model protein was examined using tryptophan intrinsic fluorescence, UV/Vis, and circular dichroism (CD) spectroscopy. Moreover, enzyme activities were analyzed by a turbidometric approach in the presence of MNPs at concentrations providing MNPs/HEWL ratios in the range of 0.04-1.25. As-synthesized MNPS were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), vibrating sample magnetometry (VSM) and the zeta potential of MNPs was measured to be 29 mV. The goal of this work was investigating the ordering or disordering effect of MNPs on protein structure at ra...

2025, Biotechnology Journal

The biodegradable polyester 3-hydroxybutyrate (3HB) polymer [P(3HB)] is intracellularly synthesized and accumulated in recombinant Escherichia coli harboring a set of polymer synthetic genes. In this study, we used native polyhydroxyalkanoate (PHA) synthases to attempt to microbially secrete 3HB homo-oligomers (3HBOs), which are widely distributed in nature as physiologically active substances such as plant growth-promoting factors and antibiotic compounds. High secretory production was observed, especially for the two PHA synthases from Aeromonas caviae and Bacillus cereus YB4. Surprisingly, an ethyl ester at the carboxy terminus (ethyl ester form) of 3HBOs was identified for most of the PHA synthases tested, as revealed by ESI-TOF-MS and NMR analyses. Next, 3HBOs with a functional carboxyl group (carboxyl form of 3HBO) were obtained by using the alcohol dehydrogenase gene (adhE)-deficient mutant strain, suggesting that the endogenous ethanol produced in E.

2025, Biotechnology Journal

The biodegradable polyester 3‐hydroxybutyrate (3HB) polymer [P(3HB)] is intracellularly synthesized and accumulated in recombinant Escherichia coli. In this study, native polyhydroxyalkanoate (PHA) synthases are used to attempt to microbially secrete 3HB homo‐oligomers (3HBOs), which are widely distributed in nature as physiologically active substances. High secretory production is observed, especially for the two PHA synthases from Aeromonas caviae and Bacillus cereus YB4. Surprisingly, an ethyl ester at the carboxy terminus (ethyl ester form) of 3HBOs is identified for most of the PHA synthases tested. Next, 3HBOs with a functional carboxyl group (carboxyl form of 3HBO) are obtained by using the alcohol dehydrogenase gene (adhE)‐deficient mutant strain, suggesting that the endogenous ethanol produced in E. coli acts as a chain transfer (CT) agent in the generation of 3HBOs. Furthermore, an in vitro polymerization assay reveals that CT agents such as ethanol and free 3HB are involv...

2025, Human Gene Therapy

The antitumor efficacy of human melanoma-associated antigen (hgp100) and chemokine CCL21 in combination with interleukin-12 (IL-12) was evaluated in a syngeneic melanoma mouse model. The rationale for this approach was based on previous studies showing that the efficacy of IL-12 therapy in melanoma patients correlated with the presence of antibodies against tumor-associated antigens. We have previously shown that application of xenogeneic human gp100 DNA (hgp100 DNA) is protective against mouse B16 melanoma. Furthermore, the chemokine CCL21 has the ability to chemoattract both dendritic cells (DCs) and T lymphocytes. We show here that intratumoral injection of IL-12-encoding DNA (IL-12 DNA) in combination with hgp100encoding DNA (hgp100 DNA) into tumor-bearing mice led to a strong antitumor effect. Coapplication of IL-12 DNA with CCL21-encoding DNA (CCL21 DNA) or recombinant CCL21 (recCCL21) protein also showed some efficacy. Triple therapy with IL-12 DNA, hgp100 DNA, and CCL21 DNA, however, showed less effect on tumor growth than double therapy with IL-12 DNA and hgp100 DNA. These findings open a new route of investigation of IL-12 and gp100 or other tumor-associated antigens in the immunotherapy of a variety of tumors.

2025, Human Gene Therapy

States, but to date no vaccine against this virus is available. We have established a new animal model, genetically targeted mice lacking a functional interferon type I receptor (IFNAR-1). These mice show an age-independent susceptibility to LACV and develop an acute encephalitis within 6 days of infection, thereby allowing the evaluation of vaccines against LACV. Taking advantage of this knockout mouse model, we have assessed the feasibility of DNA vaccination against this viral disease. Plasmid DNAs, encoding either the virus surface glycoproteins G1 and G2 or the internal nucleocapsid protein N, were used to immunize IFNAR-1deficient mice. Mice vaccinated with DNA encoding the glycoproteins G1 and G2 produced neutralizing antibodies and exhibited a high degree of protection against challenge with high doses of LACV. Depletion of CD4 1 T cells in mice vaccinated with DNA encoding G1/G2 reduced their capacity to control the infection. Virus titration and immunohistological analysis revealed that the protected mice showed no evidence of LACV particles in the brain. This indicates that the vaccine-induced immune response efficiently blocked viral spreading from the primary replication site to the brain. In contrast, immunization with DNA encoding protein N yielded only a partial protective effect that can be attributed to the cellular immune response. Taken together, this study shows that DNA vaccines can be designed to efficiently induce a protective immune response based on neutralizing antibodies and CD4 1 T cells.

2025, ACS Nano

Peripheral vascular disease (PVD) is one of the most prevalent vascular diseases in the U.S. afflicting an estimated 8 million people. Obstruction of peripheral arteries leads to insufficient nutrients and oxygen supply to extremities, which, if not treated properly, can potentially give rise to a severe condition called critical limb ischemia (CLI). CLI is associated with extremely high morbidities and mortalities. Conventional treatments such as angioplasty, atherectomy, stent implantation and bypass surgery have achieved some success in treating localized macrovascular disease but are limited by their invasiveness. An emerging alternative is the use of growth factor (delivered as genes or proteins) and cell therapy for PVD treatment. By delivering growth factors or cells to the ischemic tissue, one can stimulate the regeneration of functional vasculature network locally, re-perfuse the ischemic tissue, and thus salvage the limb. Here we review recent advance in nanomaterials, and discuss how their application can improve and facilitate growth factor or cell therapies. Specifically, nanoparticles (NPs) can serve as drug carrier and target to ischemic tissues and achieve localized and sustained release of pro-angiogenic proteins. As nonviral vectors, NPs can greatly enhance the transfection of target cells with pro-angiogenic genes with relatively fewer safety concern. Further, NPs may also be used in combination with cell therapy to enhance cell retention, cell survival and secretion of angiogenic factors. Lastly, nano/ micro fibrous vascular grafts can be engineered to better mimic the structure and composition of native vessels, and hopefully overcome many complications/limitations associated with conventional synthetic grafts.

2025, biomaterials advances

Increased use of titanium (Ti) and its alloys in implant manufacture is due to their biocompatibility and mechanical properties. However, their biological inertness must be considered. Surface modifications are essential for accelerating osteointegration and bone healing. Herein, calcium phosphate (brushite, CaHPO 4 .2H 2 O) was deposited on an additive-manufactured Ti6Al4V alloy substrate by electrochemical deposition technique. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy confirmed the presence of brushite on the Ti6Al4V substrate. Scanning electron microscopy (SEM) and cross-section micrograph observations confirmed the homogeneity of the coating's coverage, composed of microcrystals approximately 1-3 μm thick and 10 μm long. EDXS analysis revealed pure brushite stoichiometric values, and tensile adhesion tests demonstrated good adhesion to the substrate. The coating demonstrated a rapid dissolution in MES (pH 5.5) and HEPES (pH 7.4) buffer solutions. Human mesenchymal stem cells (hMSCs) cultured with brushite-coated Ti alloy in osteogenic medium showed normal proliferation and increased biomineralization with SP7 mRNA upregulation. To explore how Brushite improved bone healing, we performed liquid chromatography-tandem mass spectrometry (LC-MS/ MS)-based proteomics analysis of hMSCs secretome from co-cultures with Ti alloys, for 7 and 14 days. Brushite promoted secretion of osteogenic and bone matrix factors. Factors involved in blood clotting (e.g. FII, FV, FX), mitochondrial biogenesis, energy metabolism (e.g. mitochondrial ATP synthase), lipid metabolism (e.g. apolipoproteins) and cellular stress response (e.g. heat shock proteins) were enriched. Increased specific chromatinrelated proteins suggest chromatin's role in enhancing bone regeneration. Secretome profiling showed the unique role of brushite Ti alloys in bone regeneration, encouraging further study.

2025, The FASEB Journal

Due to its small size and particular isolating barriers, the eye is an ideal target for local therapy. Recombinant protein ocular delivery requires invasive and painful repeated injections. Alternatively, a transfected tissue might be used as a local producer of transgene-encoded therapeutic protein. We have developed a nondamaging electrically mediated plasmid delivery technique (electrotransfer) targeted to the ciliary muscle, which is used as a reservoir tissue for the long-lasting expression and secretion of therapeutic proteins. High and long-lasting reporter gene expression was observed, which was restricted to the ciliary muscle. Chimeric TNF-α soluble receptor (hTNFR-Is) electrotransfer led to elevated protein secretion in aqueous humor and to drastic inhibition of clinical and histological inflammation scores in rats with endotoxininduced uveitis. No hTNFR-Is was detected in the serum, demonstrating the local delivery of proteins using this method. Plasmid electrotransfer to the ciliary muscle, as performed in this study, did not induce any ocular pathology or structural damage. Local and sustained therapeutic protein production through ciliary muscle electrotransfer is a promising alternative to repeated intraocular protein administration for a large number of inflammatory, degenerative, or angiogenic diseases. Key words: electroporation • gene delivery • gene therapy • inflammation herapeutic proteins have a great potential to cure eye diseases. Numerous growth factors display neurotrophic properties and can influence retinal degeneration processes (1, 2). Interleukins and Th2 cytokines are used as immunomodulators in the treatment of ocular inflammations (3, 4), while blocking antibodies or soluble receptors to TNF-α are currently being tested in patients with severe refractive uveitis

2025

A double blinded, placebo-controlled pilot study to examine reduction of CD34 /CD117 /CD133 lymphoma progenitor cells and duration of remission induced by neoadjuvant valspodar in dogs with large B-cell lymphoma [version 1; referees: 1... more

2025, Clinical Chemistry

Using a specific high-performance liquid-chromatographic method, we measured norepinephrine, epinephrine, and dopamine in 24-h urine collections from 459 men and 497 women, ages 17 to 88 years. We found a significant negative correlation between age and the 24-h excretion of dopamine in men and women (P less than 0.001). Epinephrine excretion decreased with age in men (P less than 0.001). No age dependence was observed for norepinephrine (P greater than 0.2). The excretion of all three catecholamines, expressed in nmol/24 h, was significantly greater in men than in women. The differences, however, were small. With data expressed in nmol/g of creatinine, only epinephrine excretion was greater in men; norepinephrine and dopamine excretions were slightly greater in women. Also, expressed in these units, urinary excretion of norepinephrine in both sexes and of epinephrine in women was significantly positively related with age; urinary excretion of dopamine was significantly inversely re...

2025, Biomedical Signal Processing and Control

Diabetic retinopathy, a chronic disease in diabetic patients leads to Vision loss, by disabling microvascular complications, if not recognized and cured at the earlier stage. This article explores a novel and reliable method for automatic early detection of Microaneurysms (MA) in fundus images. Microaneurysms characterized by small red spots on the retina, the red lesions are symptoms of early stage of DR. Development of an automated screening system would assist an ophthalmologist in diagnosing DR at an early stage. Hence, in this paper, a novel feature extraction technique using a Local Neighborhood Differential Coherence Pattern (LNDCP) is proposed. In this method, texture characteristics needed for classification by Feed Forward Neural Network (FFNN) is captured efficiently. The performance of the algorithm is validated using experiments on Retinopathy Online Challenge (ROC) public dataset and a single real-time dataset, AGAR300. Efficiency of the algorithm is benchmarked with state-of-art approaches and a Freeresponse Receiver Operating Characteristic (FROC) score of 0.481 and 0.442 have been achieved for ROC and AGAR300 respectively.

2025, Journal of Community Genetics

We developed a video and an app for obtaining consent about allowing newborn blood spots (NBS) to be used as biospecimen resources for biobanking. Newborn screening programs test for treatable diseases and leave residual biospecimens that can be used in future research activities. We conducted focus groups and interviews with three diverse communities to determine (a) how well the consent tools worked and (b) participant familiarity with NBS. Participants preferred the video and noted that they were unaware that NBS could be used for future research. Providing information about how biospecimens could be used was a key issue.

2025, Sensors

A low-power, high-gain, and low-noise analog front-end (AFE) for wearable photoplethysmography (PPG) acquisition systems is designed and fabricated in a 0.35 μm CMOS process. A high transimpedance gain of 142 dBΩ and a low input-referred noise of only 64.2 pArms was achieved. A Sub-Hz filter was integrated using a pseudo resistor, resulting in a small silicon area. To mitigate the saturation problem caused by background light (BGL), a BGL cancellation loop and a new simple automatic gain control block are used to enhance the dynamic range and improve the linearity of the AFE. The measurement results show that a DC photocurrent component up-to-10 μA can be rejected and the PPG output swing can reach 1.42 Vpp at THD < 1%. The chip consumes a total power of 14.85 μW using a single 3.3-V power supply. In this work, the small area and efficiently integrated blocks were used to implement the PPG AFE and the silicon area is minimized to 0.8 mm × 0.8 mm.

2025

Congenital anomalies (CA) are an important cause of morbidity and mortality in infants and children. More than 100,000 children with CA are born in EU each year. The European Surveillance of Congenital Anomalies (EUROCAT) is a network of population based congenital anomaly registries in Europe currently surveying 31% of EU birth population. EUROCAT has been awarded funding for 2011-2013 as a Joint Action between EU and member states. The Joint Action EUROCAT aims to use harmonised data on CA across EU to assess prevalence of all birth outcomes, the impact of primary prevention, and developments in prenatal screening. Joint Action EUROCAT will serve as an early warning of teratogen exposures, and act as an information centre regarding clusters, and exposures to risk factors of concern, including new medicine used in pregnancy, ail pollution, swine flu vaccination, and chronic maternal diseases as obesity and diabetes.

2025, The EMBO Journal

Breast cancer is a group of heterogeneous diseases that show substantial variation in their molecular and clinical characteristics. This heterogeneity poses significant challenges not only in breast cancer management, but also in studying the biology of the disease. Recently, rapid progress has been made in understanding the genomic diversity of breast cancer. These advances led to the characterisation of a new genome-driven integrated classification of breast cancer, which substantially refines the existing classification systems currently used. The novel classification integrates molecular information on the genomic and transcriptomic landscapes of breast cancer to define 10 integrative clusters, each associated with distinct clinical outcomes and providing new insights into the underlying biology and potential molecular drivers. These findings have profound implications both for the individualisation of treatment approaches, bringing us a step closer to the realisation of personalised cancer management in breast cancer, but also provide a new framework for studying the underlying biology of each novel subtype.

2025, Theranostics

The introduction of magnetic resonance (MR)-guided radiation treatment planning has opened a new space for theranostic nanoparticles to reduce acute toxicity while improving local control. In this work, second-generation AGuIX ® nanoparticles (AGuIX-Bi) are synthesized and validated. AGuIX-Bi are shown to maintain MR positive contrast while further amplifying the radiation dose by the replacement of some Gd 3+ cations with higher Z Bi 3+ . These next-generation nanoparticles are based on the AGuIX ® platform, which is currently being evaluated in multiple Phase II clinical trials in combination with radiotherapy. Methods: In this clinically scalable methodology, AGuIX ® is used as an initial chelation platform to exchange Gd 3+ for Bi 3+ . AGuIX-Bi nanoparticles are synthesized with three ratios of Gd/Bi, each maintaining MR contrast while further amplifying radiation dose relative to Bi 3+ . Safety, efficacy, and theranostic potential of the nanoparticles were evaluated in vitro and in vivo in a human non-small cell lung cancer model. We demonstrated that increasing Bi 3+ in the nanoparticles is associated with more DNA damage and improves in vivo efficacy with a statistically significant delay in tumor growth and 33% complete regression for the largest Bi/Gd ratio tested. The addition of Bi 3+ by our synthetic method leads to nanoparticles that present slightly altered pharmacokinetics and lengthening of the period of high tumor accumulation with no observed evidence of toxicity. Conclusions: We confirmed the safety and enhanced efficacy of AGuIX-Bi with radiation therapy at the selected ratio of 30Gd/70Bi. These results provide crucial evidence towards patient translation.

2025, Applied Sciences

Language identification is the front end of multilingual speech-processing tasks. The study aims to enhance the accuracy of language identification in complex acoustic environments by proposing a multi-scale feature extraction method. This method replaces the baseline feature extraction network with a multi-scale feature extraction network (SE-Res2Net-CBAM-BILSTM) to extract multi-scale features. A multilingual cocktail party dataset was simulated, and comparative experiments were conducted with various models. The experimental results show that the proposed model achieved language identification accuracies of 97.6% for an Oriental language dataset and 75% for a multilingual cocktail party dataset Furthermore, comparative experiments show that our model outperformed three other models in the accuracy, recall, and F1 values. Finally, a comparison of different loss functions shows that the model performance was better when using focal loss.

2025, Human Gene Therapy

Numerous environmental influences have been demonstrated to enhance recombinant adeno-associated virus (rAAV) transduction. Such findings are the foundation of developing new and innovative strategies to improve the efficiency of rAAV as a gene therapy vector. Several of these environmental factors included genotoxic stresses such as UV and g irradiation as well as certain adenoviral gene products such as E4orf6. The mechanisms by which these environmental stimuli increase rAAV transduction are only partially understood but have been suggested to involve both endocytosis and uptake of virus to the nucleus, as well as conversion of single-stranded DNA viral genomes to double-stranded expressible forms. Two molecular intermediates of rAAV genomes, which have been demonstrated to correlate with transgene expression and/or the persistence of rAAV, include both replication form (Rf) monomers and dimers as well as circular intermediates. In the present study, we demonstrate that augmentation of rAAV transduction by UV irradiation and the adenoviral protein E4orf6 correlates with distinct increases in either circular or replication form intermediates, respectively. UV irradiation of primary fibroblasts at 15 J/m 2 resulted in a 15-fold induction of head-to-tail circular intermediates, with minimal induction of replication form rAAV genomes. In contrast, E4orf6-augmented rAAV transduction was correlated with the formation of replication form intermediates, with no alteration in the abundance of circular intermediates. These findings demonstrate that rAAV transduction can occur through two independent molecular pathways that convert single-stranded AAV genomes to expressible forms of DNA.

2025, Human Gene Therapy

The advancement in gene transfer technologies has greatly benefited the field of gene therapy. Nevertheless, several bottlenecks have been identified that undermine the efficacy and/or safety of the gene delivery vector, hampering clinical translation. We have gained a better understanding of how to improve the efficacy and safety of gene therapy using different synthetic biology approaches. To achieve this, we explored different strategies based de novo vector design principles, each tackling a specific bottleneck in gene therapy, either at the level of genomic integration, transgene expression or the immune response. (i) Genomic integration: For the past 25 years, development of non-viral vectors for stable gene transfer into human CD34 + hematopoietic stem/progenitor cells (HSCs) has been unsuccessful. We have overcome this bottleneck by using de novo designed hyperactive Sleeping Beauty (SB) transposase, which led to unprecedentedf stable gene transfer efficiencies in CD34 + HSC. Consequently, xeno-transplantation of these transposon-marked CD34 + HSCs into immune deficient mice yielded long-term engraftment and hematopoietic reconstitution paving the way for new transposon-based gene therapy applications. (ii) Transgene expression: To improve transgene expression for tissue-directed gene therapy, we validated a datamining algorithm that led to the identification of combinations of regulatory elements, associated with high tissuespecific expression. Incorporation of these de novo designed, synthetic regulatory elements in viral and non-viral vectors enhanced transcriptional targeting in heart or liver. Up to a 100-fold enhancement in tissue-specific expression could be achieved, depending on the promoter used, while retaining high cardiac and liver selectivity. Vector performance could be enhanced further by using synthetic codon-optimized and/or hyperactive therapeutic genes. The de novo design of these regulatory elements and synthetic transgenes improved the therapeutic index of viral and non-viral gene delivery vectors. (iii) Immune response: One of the main limitations of using AAV-based vectors is that they can evoke an AAV capsid-specific, T cell -mediated immune response. To reduce the risk of T cell-mediated immune rejection of AAV-transduced cells, we have now generated and characterized a novel ''immune stealth'' AAV vector that was specifically designed to inhibit antigen presentation. We demonstrated that T-cell activation and T-cell mediated recognition of liver cells transduced with this AAV ''immune stealth'' vector was substantially reduced which has broad implications for AAV-based gene therapy. Acknowledgments: I want to thank all of our collaborators and team-members for their valuable contributions.

2025, Human Gene Therapy

We have previously reported the preliminary safety and efficacy data of our novel gene transfer approach in six subjects with

2025, Research Square (Research Square)

This study investigated the effects of cilostazol on motor dysfunction, spinal motor neuron abnormalities, and schwannopathy in rats with diabetes. Diabetes mellitus (DM) was induced in rats via femoral intravenous streptozotocin (STZ) injection (60 mg/kg). After successful DM induction, cilostazol was administered on day 15 via oral gavage (100 mg/kg/day) for 6 weeks until sacri ce. Behavioral assays, including motor function were performed weekly. The sciatic nerve, L5 spinal cord, and spinal ventral root were collected to evaluate the expression of the glial brillary acidic protein (GFAP), myelin protein zero (P0), and choline acetyltransferase (ChAT) by immuno uorescence and Western blotting. DM rats displayed decreased running speeds, running distance, and toe spread but increased foot pressure. In addition, loss of non-myelinating Schwann cells and myelin sheaths was observed in the sciatic nerve and L5 spinal ventral root. Reduced numbers of motor neurons were also found in the L5 spinal ventral horn. Cilostazol administration signi cantly potentiated running speed and distance, increased hind paw toe spread, and decreased foot pressure. In the sciatic nerve and L5 spinal ventral root, cilostazol treatment signi cantly improved non-myelinated Schwann cells and increased myelin mass. ChAT expression in motor neurons in the spinal ventral horn was improved, but not signi cantly. Cilostazol administration may protect sensorimotor function in diabetic rats.

2025, Clinical Chemistry

Background: Salt-sensitive (SS) hypertension affects >30 million Americans and is often associated with low plasma renin activity. We tested the diagnostic validity of several candidate genes for SS and low-renin hypertension.Methods: In Japanese patients with newly diagnosed, untreated hypertension (n = 184), we studied polymorphisms in 10 genes, including G protein–coupled receptor kinase type 4 (GRK4), some variations of which are associated with hypertension and impair D1 receptor (D1R)-inhibited renal sodium transport. We used the multifactor dimensionality reduction method to determine the genotype associated with salt sensitivity (≥10% increase in blood pressure with high sodium intake) or low renin. To determine whether the GRK4 genotype is associated with impaired D1R function, we tested the natriuretic effect of docarpamine, a dopamine prodrug, in normotensive individuals with or without GRK4 polymorphisms (n = 18).Results: A genetic model based on GRK4 R65L, GRK4 A142V...

2025, Signal Transduction and Targeted Therapy

2025, 2019 IEEE 19th International Conference on Bioinformatics and Bioengineering (BIBE)

This paper evaluates the usage of matching pursuit (MP) features of electroencephalographic (EEG) signals and classification techniques on automatic absence seizure detection. Absence epileptic seizures are neurological disorders which are manifested as abnormal EEG patterns. Matching pursuit algorithm is able to decompose a signal into components with specific time-frequency characteristics. It is a robust technique especially when there is complex, multicomponent signal. In the present study, a clinical dataset containing 40 annotated absence seizures in long-term EEG recordings from pediatric epileptic patients (with age 6.0±2.9 years) was analyzed. The extracted MP features fed an automatic classification schema which achieved a time window based discrimination accuracy of 98.5%. As indicated by the study's results, the proposed features and analysis methods can be a promising addition to the area of automatic absence seizures detection.