Mihai Covasa - Academia.edu (original) (raw)
Papers by Mihai Covasa
Frontiers in immunology, Mar 4, 2024
COVID-19 pandemic has caused an unprecedented worldwide health and socioeconomic crisis leading t... more COVID-19 pandemic has caused an unprecedented worldwide health and socioeconomic crisis leading to more than 768 million cases of viral infections, of which approximately 7 million deaths and 13,490,832,730 vaccine doses administered globally (1). The pandemic was caused by SARS-CoV-2, severe acute respiratory syndrome coronavirus-2 which infects the host by invading cells via ACE2-angiotensin-converting enzyme 2 (2). Although the respiratory tract is the site of entry and infection of SARS-CoV-2, COVID-19 is a complex disease, affecting the cardiovascular, renal, hematological, gastrointestinal, and central nervous systems, and can present a wide severity spectrum, from asymptomatic to severe, moderate or mild symptoms. The occurrence of acute COVID-19 last from 1-2 weeks in mild cases and up to 12 weeks for the most severe ones, based on factors such as age, symptoms, comorbidities, vaccination status, access to treatment and medical services (3). More than half of the infected individuals are presented with persistent symptoms even longer than four weeks after the onset of first clinical signs, a condition defined as post-acute sequelae of COVID-19 (PASC). The presence of clinical symptoms in infected individuals that continue at least three months after the onset of disease or with new symptoms that last for more than two months with no other explanation and that cannot be associated with other existing pathologies has been defined as long COVID-19 (L-C19) (4). The National Institute for Health and Care Excellence (NICE) classifies L-C19 in two categories: 1) "ongoing symptomatic C19" with symptoms that persist from 4 to 12 weeks and 2) "post C19" with persisting symptoms beyond 12 weeks after disease onset. Several other terms have been used based on the length and persistence of symptoms to define L-C19, such as "post-acute sequelae of SARS-CoV-2 infection", "persistent C19 symptoms", "post C19 syndrome" (PCS), "long haulers", or "post C19 manifestations" (5, 6) (Table 1). In L-C19, the virus is no longer present in the nasal cavity (7), however, viral protein and/or RNA has been detected in the reproductive and cardiovascular system, brain, muscles, eyes, olfactory mucosa, lymph nodes, appendix, breast, hepatic and lung tissue, plasma, intestinal microbiome, and urine (8, 9). 2 Long COVID-19 symptoms and predictors Given the wide spectrum of the L-C19 clinical symptomatology, establishing with certainty the syndrome, clinical manifestations, pathogenic factors, or its time framework, had proved challenging. The most common and representative symptoms of L-C19 include fatigue or muscle weakness, malaise, dyspnea, headache, dizziness or "brain fog", depression, irritability, frustration, insomnia, and many other neurological disorders (10, 11). Other symptoms are related to cardiac, digestive, respiratory, reproduction, or dermatologic disorders. A recent meta-analysis study showed that the five most relevant physiological signs are fatigue, headache, deficit of attention, hair loss and dyspnea, followed by skin rashes, palpitations, and diarrhea (12), with recurrent spikes of fever as common symptom, but higher than observed after common infections, such as Epstein-Barr virus or influenza (13). The clinical presentation and symptomatology of L-C19 is similar with that of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) (14), a known complicated illness with 4-6 months of fatigue and exhaustion, reduced daily activity and post-exertional malaise (15). Other common symptoms may include myalgia, muscle weakness, headache, sleep disorders, neurocognitive and psychiatric manifestations, anorexia or autonomic manifestations (orthostatic intolerance, cardiovascular, respiratory, gastro-intestinal, or gastrourinary) (16) Compared with influenza, sequelae of L-C19 were higher in terms of anxiety and mood disorders, insomnia, and dementia (17). There have been over 200 symptoms associated with L-C19, with the most representative being depicted in Figure 1. Due to the overproduction of pro-inflammatory cytokines, C19 is not a usual viral pneumonia, but rather one with major consequences on the central and peripheral nervous system, cardiovascular, respiratory, urinary, immune system or on metabolic functions (11). For example, Østergaard et al. using scanning microscopy reported the presence of SARS-CoV-2 particles in the endothelium of lung, heart, kidney, brain or skin of C19 patients, with capillary changes and inflammation (18). It appears that L-C19 manifestation does not usually depend on the severity of the acute COVID-19 illness. In a 14-month study de Miranda et al. showed that most patients (75.4%) who experienced L-C19 had moderate infections and only 33.1% had been severe (19). Similar results were observed by Sugyiama et al. who reported that 49.5% from the patients identified with L-C19 were mild cases (2). Unfortunately, due to the multiple symptomatology and its undefined nature, it is difficult to detect L-C19 through laboratory findings. Thus, guidelines and regulations would be of great benefit in identifying L-C19. To this end, Roth & Gadebusch-Bondio proposed, in addition to conventional measures, presentation of cases, symptoms, and side effects through mass media platforms that are easily accessible globally (20). This could facilitate a more rapid selfidentification of L-C19 symptoms, thus enhancing the possibility for treatment in a much shorter time. Approximately half of the individuals infected at some point with SARS-CoV-2 developed L-C19. Exhaustion, cognitive TABLE 1 Types of long-COVID.
International Journal of Molecular Sciences, Jul 6, 2022
Metabolites
Given the worldwide high prevalence of type 2 diabetes, the prevention and control of this diseas... more Given the worldwide high prevalence of type 2 diabetes, the prevention and control of this disease has become an urgent priority. In this research, we report the results from a cross-sectional study conducted in the counties of Suceava and Iasi, northeast of Romania, on 587 patients with type 2 diabetes and 264 patients with prediabetes. By employing a factor analysis (principal component) on 14 food groups followed by varimax orthogonal rotation, three dietary patterns were identified for each group. In prediabetes, a low adherence to a specific dietary pattern (1 and 2) was associated with lower fasting plasma glucose, blood pressure and serum insulin, compared to increased adherence. In patients with diabetes, a low adherence to Pattern 1 was associated with lower systolic blood pressures, while a low adherence to Pattern 3 was associated with a lower HbA1c, compared to high adherence. Statistically significant differences between the groups were observed for fats and oils, fish ...
Nutrients
Dyslipidemia is a multifaceted condition with various genetic and environmental factors contribut... more Dyslipidemia is a multifaceted condition with various genetic and environmental factors contributing to its pathogenesis. Further, this condition represents an important risk factor for its related sequalae including cardiovascular diseases (CVD) such as coronary artery disease (CAD) and stroke. Emerging evidence has shown that gut microbiota and their metabolites can worsen or protect against the development of dyslipidemia. Although there are currently numerous treatment modalities available including lifestyle modification and pharmacologic interventions, there has been promising research on dyslipidemia that involves the benefits of modulating gut microbiota in treating alterations in lipid metabolism. In this review, we examine the relationship between gut microbiota and dyslipidemia, the impact of gut microbiota metabolites on the development of dyslipidemia, and the current research on dietary interventions, prebiotics, probiotics, synbiotics and microbiota transplant as ther...
Frontiers in Medicine
Fecal microbiota transplant (FMT) is a therapeutic method that aims to restore normal gut microbi... more Fecal microbiota transplant (FMT) is a therapeutic method that aims to restore normal gut microbial composition in recipients. Currently, FMT is approved in the USA to treat recurrent and refractory Clostridioides difficile infection and has been shown to have great efficacy. As such, significant research has been directed toward understanding the potential role of FMT in other conditions associated with gut microbiota dysbiosis such as obesity, type 2 diabetes mellitus, metabolic syndrome, neuropsychiatric disorders, inflammatory bowel disease, irritable bowel syndrome, decompensated cirrhosis, cancers and graft-versus-host disease. This review examines current updates and efficacy of FMT in treating conditions other than Clostridioides difficile infection. Further, protocols for administration of FMT are also discussed including storage of fecal samples in stool banks, inclusion/exclusion criteria for donors, fecal sample preparation and methods of treatment administration. Overal...
Gels
The benefits of using biopolymers for the development of films and coatings are well known. The e... more The benefits of using biopolymers for the development of films and coatings are well known. The enrichment of these material properties through various natural additions has led to their applicability in various fields. Essential oils, which are well-known for their beneficial properties, are widely used as encapsulating agents in films based on biopolymers. In this study, we developed biopolymer-based films and tested their properties following the addition of 7.5% and 15% (w/v) essential oils of lemon, orange, grapefruit, cinnamon, clove, chamomile, ginger, eucalyptus or mint. The samples were tested immediately after development and after one year of storage in order to examine possible long-term property changes. All films showed reductions in mass, thickness and microstructure, as well as mechanical properties. The most considerable variations in physical properties were observed in the 7.5% lemon oil sample and the 15% grapefruit oil sample, with the largest reductions in mass...
International Journal of Molecular Sciences
Recent work has demonstrated the ability of the gut microbiota (GM) to alter the expression and r... more Recent work has demonstrated the ability of the gut microbiota (GM) to alter the expression and release of gut peptides that control appetite and regulate energy homeostasis. However, little is known about the neuronal response of these hormones in germ-free (GF) animals, especially leptin, which is strikingly low in these animals. Therefore, we aimed to determine the response to exogenous leptin in GF mice as compared to conventionally raised (CONV-R) mice. Specifically, we injected and measured serum leptin in both GF and CONV-R mice and measured expression of orexigenic and anorexigenic peptides NPY, AgRP, POMC, and CART in the hypothalamus and hindbrain to examine whether the GM has an impact on central nervous system regulation of energy homeostasis. We found that GF mice had a significant increase in hypothalamic NPY and AgRP mRNA expression and a decrease in hindbrain NPY and AgRP mRNA, while mRNA expression of POMC and CART remained unchanged. Administration of leptin normal...
International Journal of Molecular Sciences
Parkinson’s disease (PD), the second most common neurodegenerative disorder worldwide, is charact... more Parkinson’s disease (PD), the second most common neurodegenerative disorder worldwide, is characterized by dopaminergic neuron degeneration and α-synuclein aggregation in the substantia nigra pars compacta of the midbrain. Emerging evidence has shown that dietary intake affects the microbial composition in the gut, which in turn contributes to, or protects against, the degeneration of dopaminergic neurons in affected regions of the brain. More specifically, the Mediterranean diet and Western diet, composed of varying amounts of proteins, carbohydrates, and fats, exert contrasting effects on PD pathophysiology via alterations in the gut microbiota and dopamine levels. Interestingly, the negative changes in the gut microbiota of patients with PD parallel changes that are seen in individuals that consume a Western diet, and are opposite to those that adhere to a Mediterranean diet. In this review, we first examine the role of prominent food groups on dopamine bioavailability, how they ...
Biomedicines
Dopamine is a neurotransmitter that plays a critical role both peripherally and centrally in vita... more Dopamine is a neurotransmitter that plays a critical role both peripherally and centrally in vital functions such as cognition, reward, satiety, voluntary motor movements, pleasure, and motivation. Optimal dopamine bioavailability is essential for normal brain functioning and protection against the development of neurological diseases. Emerging evidence shows that gut microbiota have significant roles in maintaining adequate concentrations of dopamine via intricate, bidirectional communication known as the microbiota-gut-brain axis. The vagus nerve, immune system, hypothalamus–pituitary–adrenal axis, and microbial metabolites serve as important mediators of the reciprocal microbiota-gut-brain signaling. Furthermore, gut microbiota contain intrinsic enzymatic activity that is highly involved in dopamine metabolism, facilitating dopamine synthesis as well as its metabolite breakdown. This review examines the relationship between key genera of gut microbiota such as Prevotella, Bactero...
Nutrients
The coronavirus disease 2019 (COVID-19) has caused a pandemic and upheaval that health authoritie... more The coronavirus disease 2019 (COVID-19) has caused a pandemic and upheaval that health authorities and citizens around the globe are still grappling with to this day. While public health measures, vaccine development, and new therapeutics have made great strides in understanding and managing the pandemic, there has been an increasing focus on the potential roles of diet and supplementation in disease prevention and adjuvant treatment. In the literature, the impact of nutrition on other respiratory illnesses, including the common cold, pneumonia, and influenza, has been widely demonstrated in both animal and human models. However, there is much less research on the impact related to COVID-19. The present study discusses the potential uses of diets, vitamins, and supplements, including the Mediterranean diet, glutathione, zinc, and traditional Chinese medicine, in the prevention of infection and severe illness. The evidence demonstrating the efficacy of diet supplementation on infecti...
Pharmaceutics, 2022
It has become increasingly apparent that defective insulin signaling may increase the risk for de... more It has become increasingly apparent that defective insulin signaling may increase the risk for developing Alzheimer’s disease (AD), influence neurodegeneration through promotion of amyloid formation or by increasing inflammatory responses to intraneuronal β-amyloid. Recent work has demonstrated that hyperglycemia is linked to cognitive decline, with elevated levels of glucose causing oxidative stress in vulnerable tissues such as the brain. The ability of β-amyloid peptide to form β-sheet-rich aggregates and induce apoptosis has made amyloid fibrils a leading target for the development of novel pharmacotherapies used in managing and treatment of neuropathological conditions such as AD-related cognitive decline. Additionally, deposits of β-sheets folded amylin, a glucose homeostasis regulator, are also present in diabetic patients. Thus, therapeutic compounds capable of reducing intracellular protein aggregation in models of neurodegenerative disorders may prove useful in amelioratin...
International Journal of Molecular Sciences, 2022
Severe periodontitis, a destructive inflammatory disease of the supporting tissues of the teeth, ... more Severe periodontitis, a destructive inflammatory disease of the supporting tissues of the teeth, ranks sixth in terms of global spread, affecting about 11% of the population. Metalloproteinases (MMPs) are extracellular matrix (ECM) macromolecules that are important in cellular development and morphogenesis, and they are capable of activating growth factors in their proximity, cell surface receptors, and adhesion molecules. MMPs are part of a major family of zinc-dependent endopeptidases, and their activity is modulated and regulated by certain inhibitors known as tissue metalloproteinase inhibitors (TIMPs). Because type I collagen is the major component of the periodontal extracellular matrix, special attention has been paid to the role of collagenases, especially MMP-8 and MMP-13 and gelatinases, MMP-2 and MMP-9, in periodontal diseases. In fact, MMP-8 (or collagenase 2) is currently one of the most promising biomarkers for periodontitis in oral fluids. Among them, salivary MMP-9 h...
Nutrients, 2021
The gut microbiota has been linked to the emergence of obesity, metabolic syndrome and the onset ... more The gut microbiota has been linked to the emergence of obesity, metabolic syndrome and the onset of type 2 diabetes through decreased glucose tolerance and insulin resistance. Uncontrolled diabetes can lead to serious health consequences such as impaired kidney function, blindness, stroke, myocardial infarction and lower limb amputation. Despite a variety of treatments currently available, cases of diabetes and resulting complications are on the rise. One promising new approach to diabetes focuses on modulating the gut microbiota with probiotics, prebiotics, synbiotics and fecal microbial transplantation. Differences in gut microbiota composition have been observed in preclinical animal models as well as patients with type 2 diabetes and complications such as diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, cerebrovascular disease, coronary heart disease and peripheral artery disease compared to healthy controls. Severity of gut microbiota dysbiosis was associated wi...
Polymers, 2021
Research regarding the use of biopolymers has been of great interest to scientists, the medical c... more Research regarding the use of biopolymers has been of great interest to scientists, the medical community, and the industry especially in recent years. Initially used for food applications, the special properties extended their use to the pharmaceutical and medical industries. The practical applications of natural drug encapsulation materials have emerged as a result of the benefits of the use of biopolymers as edible coatings and films in the food industry. This review highlights the use of polysaccharides in the pharmaceutical industries and as encapsulation materials for controlled drug delivery systems including probiotics, focusing on their development, various applications, and benefits. The paper provides evidence in support of research studying the use of biopolymers in the development of new drug delivery systems, explores the challenges and limitations in integrating polymer-derived materials with product delivery optimization, and examines the host biological/metabolic pa...
United Kingdom reported the emergence of a new and highly transmissible SARS-CoV-2 variant B.1.1.... more United Kingdom reported the emergence of a new and highly transmissible SARS-CoV-2 variant B.1.1.7. that rapidly spread to other contries. The impact of this new mutation that occurs in the S protein, on infectivity, virulence and current vaccine effectiveness is still under evaluation. We have identified the first cases of the B.1.1.7 variant in samples collected from Romanian patients, of which one was traced to the UK region where the new variant was originally sequenced. Mutations in the Nsp3 protein, N844S and D455N and L15F in Orf3a were also detected, indicating common ancestry with UK strains as well as remote connections with strains from Nagasaki, Japan. These results indicate, for the first time, the presence and characteristics of the new variant B.1.1.7 in Romania and underscore the need for increased genomic sequencing in confirmed COVID-19 patients.
Frontiers in Microbiology, 2021
Romania officially declared its first Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2... more Romania officially declared its first Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) case on February 26, 2020. The first and largest coronavirus disease 2019 (COVID-19) outbreak in Romania was recorded in Suceava, North-East region of the country, and originated at the Suceava regional county hospital. Following sheltering-in-place measures, infection rates decreased, only to rise again after relaxation of measures. This study describes the spread of SARS-CoV-2 in Suceava and other parts of Romania and analyses the mutations and their association with clinical manifestation of the disease during the period of COVID-19 outbreak. Sixty-two samples were sequenced via high-throughput platform and screened for variants. For selected mutations, putative biological significance was assessed, and their effects on disease severity. Phylogenetic analysis was conducted on Romanian genomes (n = 112) and on sequences originating from Europe, United Kingdom, Africa, Asia, South, an...
Biology, 2021
The ongoing COVID-19 pandemic follows an unpredictable evolution, driven by both host-related fac... more The ongoing COVID-19 pandemic follows an unpredictable evolution, driven by both host-related factors such as mobility, vaccination status, and comorbidities and by pathogen-related ones. The pathogenicity of its causative agent, SARS-CoV-2 virus, relates to the functions of the proteins synthesized intracellularly, as guided by viral RNA. These functions are constantly altered through mutations resulting in increased virulence, infectivity, and antibody-evasion abilities. Well-characterized mutations in the spike protein, such as D614G, N439K, Δ69–70, E484K, or N501Y, are currently defining specific variants; however, some less studied mutations outside the spike region, such as p. 3691 in NSP6, p. 9659 in ORF-10, 8782C > T in ORF-1ab, or 28144T > C in ORF-8, have been proposed for altering SARS-CoV-2 virulence and pathogenicity. Therefore, in this study, we focused on A105V mutation of SARS-CoV-2 ORF7a accessory protein, which has been associated with severe COVID-19 clinica...
Antibiotics, 2021
Periodontal disease is an oral infectious and inflammatory disease caused by microorganisms that ... more Periodontal disease is an oral infectious and inflammatory disease caused by microorganisms that determine the host-mediated destruction of soft and hard periodontal tissues, which ultimately leads to tooth loss. Periodontitis affects a large part of the population, with various degrees of severity. Treatment consists of etiologic therapy: the removal of biofilm through mechanical debridement plus microbial elimination by supplementary measures. Antibiotic administration, either systemically or through local delivery, has been shown to improve clinical outcomes after mechanical periodontal treatment. Clindamycin is a lincosamide with a broad spectrum, being active against aerobic, anaerobic, and β-lactamase-producing bacteria. This antibiotic offers several advantages and some disadvantages and has been used in periodontal treatment both systemically and locally with various degrees of success. Among the properties that recommend it for periodontal treatment is the bacteriostatic ef...
Journal of Clinical Medicine, 2021
Periodontitis is one of the most common immune-mediated inflammatory conditions resulting in prog... more Periodontitis is one of the most common immune-mediated inflammatory conditions resulting in progressive destruction of periodontium. Metalloproteinase-9 (MMP-9), an enzyme that is involved in the degradation of gelatin and collagen and present in the gingival crevicular fluid, is markedly increased in periodontitis. The aim of the study is to evaluate the effects of periodontal treatment either alone or in combination with orthodontic treatment on MMP-9 levels. In this study, 60 individuals were subjected to periodontal treatment (PD) or periodontal treatment combined with orthodontic treatment (POD). Both periodontal and periodontal plus orthodontic treatments significantly improved clinical parameters and lowered MMP-9 levels compared to control group. However, the combination of periodontal with orthodontic treatment further improved clinical parameters and enhanced the lowering effect on MMP-9 levels compared to periodontal or control groups alone. Finally, the degree of malocc...
Frontiers in immunology, Mar 4, 2024
COVID-19 pandemic has caused an unprecedented worldwide health and socioeconomic crisis leading t... more COVID-19 pandemic has caused an unprecedented worldwide health and socioeconomic crisis leading to more than 768 million cases of viral infections, of which approximately 7 million deaths and 13,490,832,730 vaccine doses administered globally (1). The pandemic was caused by SARS-CoV-2, severe acute respiratory syndrome coronavirus-2 which infects the host by invading cells via ACE2-angiotensin-converting enzyme 2 (2). Although the respiratory tract is the site of entry and infection of SARS-CoV-2, COVID-19 is a complex disease, affecting the cardiovascular, renal, hematological, gastrointestinal, and central nervous systems, and can present a wide severity spectrum, from asymptomatic to severe, moderate or mild symptoms. The occurrence of acute COVID-19 last from 1-2 weeks in mild cases and up to 12 weeks for the most severe ones, based on factors such as age, symptoms, comorbidities, vaccination status, access to treatment and medical services (3). More than half of the infected individuals are presented with persistent symptoms even longer than four weeks after the onset of first clinical signs, a condition defined as post-acute sequelae of COVID-19 (PASC). The presence of clinical symptoms in infected individuals that continue at least three months after the onset of disease or with new symptoms that last for more than two months with no other explanation and that cannot be associated with other existing pathologies has been defined as long COVID-19 (L-C19) (4). The National Institute for Health and Care Excellence (NICE) classifies L-C19 in two categories: 1) "ongoing symptomatic C19" with symptoms that persist from 4 to 12 weeks and 2) "post C19" with persisting symptoms beyond 12 weeks after disease onset. Several other terms have been used based on the length and persistence of symptoms to define L-C19, such as "post-acute sequelae of SARS-CoV-2 infection", "persistent C19 symptoms", "post C19 syndrome" (PCS), "long haulers", or "post C19 manifestations" (5, 6) (Table 1). In L-C19, the virus is no longer present in the nasal cavity (7), however, viral protein and/or RNA has been detected in the reproductive and cardiovascular system, brain, muscles, eyes, olfactory mucosa, lymph nodes, appendix, breast, hepatic and lung tissue, plasma, intestinal microbiome, and urine (8, 9). 2 Long COVID-19 symptoms and predictors Given the wide spectrum of the L-C19 clinical symptomatology, establishing with certainty the syndrome, clinical manifestations, pathogenic factors, or its time framework, had proved challenging. The most common and representative symptoms of L-C19 include fatigue or muscle weakness, malaise, dyspnea, headache, dizziness or "brain fog", depression, irritability, frustration, insomnia, and many other neurological disorders (10, 11). Other symptoms are related to cardiac, digestive, respiratory, reproduction, or dermatologic disorders. A recent meta-analysis study showed that the five most relevant physiological signs are fatigue, headache, deficit of attention, hair loss and dyspnea, followed by skin rashes, palpitations, and diarrhea (12), with recurrent spikes of fever as common symptom, but higher than observed after common infections, such as Epstein-Barr virus or influenza (13). The clinical presentation and symptomatology of L-C19 is similar with that of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) (14), a known complicated illness with 4-6 months of fatigue and exhaustion, reduced daily activity and post-exertional malaise (15). Other common symptoms may include myalgia, muscle weakness, headache, sleep disorders, neurocognitive and psychiatric manifestations, anorexia or autonomic manifestations (orthostatic intolerance, cardiovascular, respiratory, gastro-intestinal, or gastrourinary) (16) Compared with influenza, sequelae of L-C19 were higher in terms of anxiety and mood disorders, insomnia, and dementia (17). There have been over 200 symptoms associated with L-C19, with the most representative being depicted in Figure 1. Due to the overproduction of pro-inflammatory cytokines, C19 is not a usual viral pneumonia, but rather one with major consequences on the central and peripheral nervous system, cardiovascular, respiratory, urinary, immune system or on metabolic functions (11). For example, Østergaard et al. using scanning microscopy reported the presence of SARS-CoV-2 particles in the endothelium of lung, heart, kidney, brain or skin of C19 patients, with capillary changes and inflammation (18). It appears that L-C19 manifestation does not usually depend on the severity of the acute COVID-19 illness. In a 14-month study de Miranda et al. showed that most patients (75.4%) who experienced L-C19 had moderate infections and only 33.1% had been severe (19). Similar results were observed by Sugyiama et al. who reported that 49.5% from the patients identified with L-C19 were mild cases (2). Unfortunately, due to the multiple symptomatology and its undefined nature, it is difficult to detect L-C19 through laboratory findings. Thus, guidelines and regulations would be of great benefit in identifying L-C19. To this end, Roth & Gadebusch-Bondio proposed, in addition to conventional measures, presentation of cases, symptoms, and side effects through mass media platforms that are easily accessible globally (20). This could facilitate a more rapid selfidentification of L-C19 symptoms, thus enhancing the possibility for treatment in a much shorter time. Approximately half of the individuals infected at some point with SARS-CoV-2 developed L-C19. Exhaustion, cognitive TABLE 1 Types of long-COVID.
International Journal of Molecular Sciences, Jul 6, 2022
Metabolites
Given the worldwide high prevalence of type 2 diabetes, the prevention and control of this diseas... more Given the worldwide high prevalence of type 2 diabetes, the prevention and control of this disease has become an urgent priority. In this research, we report the results from a cross-sectional study conducted in the counties of Suceava and Iasi, northeast of Romania, on 587 patients with type 2 diabetes and 264 patients with prediabetes. By employing a factor analysis (principal component) on 14 food groups followed by varimax orthogonal rotation, three dietary patterns were identified for each group. In prediabetes, a low adherence to a specific dietary pattern (1 and 2) was associated with lower fasting plasma glucose, blood pressure and serum insulin, compared to increased adherence. In patients with diabetes, a low adherence to Pattern 1 was associated with lower systolic blood pressures, while a low adherence to Pattern 3 was associated with a lower HbA1c, compared to high adherence. Statistically significant differences between the groups were observed for fats and oils, fish ...
Nutrients
Dyslipidemia is a multifaceted condition with various genetic and environmental factors contribut... more Dyslipidemia is a multifaceted condition with various genetic and environmental factors contributing to its pathogenesis. Further, this condition represents an important risk factor for its related sequalae including cardiovascular diseases (CVD) such as coronary artery disease (CAD) and stroke. Emerging evidence has shown that gut microbiota and their metabolites can worsen or protect against the development of dyslipidemia. Although there are currently numerous treatment modalities available including lifestyle modification and pharmacologic interventions, there has been promising research on dyslipidemia that involves the benefits of modulating gut microbiota in treating alterations in lipid metabolism. In this review, we examine the relationship between gut microbiota and dyslipidemia, the impact of gut microbiota metabolites on the development of dyslipidemia, and the current research on dietary interventions, prebiotics, probiotics, synbiotics and microbiota transplant as ther...
Frontiers in Medicine
Fecal microbiota transplant (FMT) is a therapeutic method that aims to restore normal gut microbi... more Fecal microbiota transplant (FMT) is a therapeutic method that aims to restore normal gut microbial composition in recipients. Currently, FMT is approved in the USA to treat recurrent and refractory Clostridioides difficile infection and has been shown to have great efficacy. As such, significant research has been directed toward understanding the potential role of FMT in other conditions associated with gut microbiota dysbiosis such as obesity, type 2 diabetes mellitus, metabolic syndrome, neuropsychiatric disorders, inflammatory bowel disease, irritable bowel syndrome, decompensated cirrhosis, cancers and graft-versus-host disease. This review examines current updates and efficacy of FMT in treating conditions other than Clostridioides difficile infection. Further, protocols for administration of FMT are also discussed including storage of fecal samples in stool banks, inclusion/exclusion criteria for donors, fecal sample preparation and methods of treatment administration. Overal...
Gels
The benefits of using biopolymers for the development of films and coatings are well known. The e... more The benefits of using biopolymers for the development of films and coatings are well known. The enrichment of these material properties through various natural additions has led to their applicability in various fields. Essential oils, which are well-known for their beneficial properties, are widely used as encapsulating agents in films based on biopolymers. In this study, we developed biopolymer-based films and tested their properties following the addition of 7.5% and 15% (w/v) essential oils of lemon, orange, grapefruit, cinnamon, clove, chamomile, ginger, eucalyptus or mint. The samples were tested immediately after development and after one year of storage in order to examine possible long-term property changes. All films showed reductions in mass, thickness and microstructure, as well as mechanical properties. The most considerable variations in physical properties were observed in the 7.5% lemon oil sample and the 15% grapefruit oil sample, with the largest reductions in mass...
International Journal of Molecular Sciences
Recent work has demonstrated the ability of the gut microbiota (GM) to alter the expression and r... more Recent work has demonstrated the ability of the gut microbiota (GM) to alter the expression and release of gut peptides that control appetite and regulate energy homeostasis. However, little is known about the neuronal response of these hormones in germ-free (GF) animals, especially leptin, which is strikingly low in these animals. Therefore, we aimed to determine the response to exogenous leptin in GF mice as compared to conventionally raised (CONV-R) mice. Specifically, we injected and measured serum leptin in both GF and CONV-R mice and measured expression of orexigenic and anorexigenic peptides NPY, AgRP, POMC, and CART in the hypothalamus and hindbrain to examine whether the GM has an impact on central nervous system regulation of energy homeostasis. We found that GF mice had a significant increase in hypothalamic NPY and AgRP mRNA expression and a decrease in hindbrain NPY and AgRP mRNA, while mRNA expression of POMC and CART remained unchanged. Administration of leptin normal...
International Journal of Molecular Sciences
Parkinson’s disease (PD), the second most common neurodegenerative disorder worldwide, is charact... more Parkinson’s disease (PD), the second most common neurodegenerative disorder worldwide, is characterized by dopaminergic neuron degeneration and α-synuclein aggregation in the substantia nigra pars compacta of the midbrain. Emerging evidence has shown that dietary intake affects the microbial composition in the gut, which in turn contributes to, or protects against, the degeneration of dopaminergic neurons in affected regions of the brain. More specifically, the Mediterranean diet and Western diet, composed of varying amounts of proteins, carbohydrates, and fats, exert contrasting effects on PD pathophysiology via alterations in the gut microbiota and dopamine levels. Interestingly, the negative changes in the gut microbiota of patients with PD parallel changes that are seen in individuals that consume a Western diet, and are opposite to those that adhere to a Mediterranean diet. In this review, we first examine the role of prominent food groups on dopamine bioavailability, how they ...
Biomedicines
Dopamine is a neurotransmitter that plays a critical role both peripherally and centrally in vita... more Dopamine is a neurotransmitter that plays a critical role both peripherally and centrally in vital functions such as cognition, reward, satiety, voluntary motor movements, pleasure, and motivation. Optimal dopamine bioavailability is essential for normal brain functioning and protection against the development of neurological diseases. Emerging evidence shows that gut microbiota have significant roles in maintaining adequate concentrations of dopamine via intricate, bidirectional communication known as the microbiota-gut-brain axis. The vagus nerve, immune system, hypothalamus–pituitary–adrenal axis, and microbial metabolites serve as important mediators of the reciprocal microbiota-gut-brain signaling. Furthermore, gut microbiota contain intrinsic enzymatic activity that is highly involved in dopamine metabolism, facilitating dopamine synthesis as well as its metabolite breakdown. This review examines the relationship between key genera of gut microbiota such as Prevotella, Bactero...
Nutrients
The coronavirus disease 2019 (COVID-19) has caused a pandemic and upheaval that health authoritie... more The coronavirus disease 2019 (COVID-19) has caused a pandemic and upheaval that health authorities and citizens around the globe are still grappling with to this day. While public health measures, vaccine development, and new therapeutics have made great strides in understanding and managing the pandemic, there has been an increasing focus on the potential roles of diet and supplementation in disease prevention and adjuvant treatment. In the literature, the impact of nutrition on other respiratory illnesses, including the common cold, pneumonia, and influenza, has been widely demonstrated in both animal and human models. However, there is much less research on the impact related to COVID-19. The present study discusses the potential uses of diets, vitamins, and supplements, including the Mediterranean diet, glutathione, zinc, and traditional Chinese medicine, in the prevention of infection and severe illness. The evidence demonstrating the efficacy of diet supplementation on infecti...
Pharmaceutics, 2022
It has become increasingly apparent that defective insulin signaling may increase the risk for de... more It has become increasingly apparent that defective insulin signaling may increase the risk for developing Alzheimer’s disease (AD), influence neurodegeneration through promotion of amyloid formation or by increasing inflammatory responses to intraneuronal β-amyloid. Recent work has demonstrated that hyperglycemia is linked to cognitive decline, with elevated levels of glucose causing oxidative stress in vulnerable tissues such as the brain. The ability of β-amyloid peptide to form β-sheet-rich aggregates and induce apoptosis has made amyloid fibrils a leading target for the development of novel pharmacotherapies used in managing and treatment of neuropathological conditions such as AD-related cognitive decline. Additionally, deposits of β-sheets folded amylin, a glucose homeostasis regulator, are also present in diabetic patients. Thus, therapeutic compounds capable of reducing intracellular protein aggregation in models of neurodegenerative disorders may prove useful in amelioratin...
International Journal of Molecular Sciences, 2022
Severe periodontitis, a destructive inflammatory disease of the supporting tissues of the teeth, ... more Severe periodontitis, a destructive inflammatory disease of the supporting tissues of the teeth, ranks sixth in terms of global spread, affecting about 11% of the population. Metalloproteinases (MMPs) are extracellular matrix (ECM) macromolecules that are important in cellular development and morphogenesis, and they are capable of activating growth factors in their proximity, cell surface receptors, and adhesion molecules. MMPs are part of a major family of zinc-dependent endopeptidases, and their activity is modulated and regulated by certain inhibitors known as tissue metalloproteinase inhibitors (TIMPs). Because type I collagen is the major component of the periodontal extracellular matrix, special attention has been paid to the role of collagenases, especially MMP-8 and MMP-13 and gelatinases, MMP-2 and MMP-9, in periodontal diseases. In fact, MMP-8 (or collagenase 2) is currently one of the most promising biomarkers for periodontitis in oral fluids. Among them, salivary MMP-9 h...
Nutrients, 2021
The gut microbiota has been linked to the emergence of obesity, metabolic syndrome and the onset ... more The gut microbiota has been linked to the emergence of obesity, metabolic syndrome and the onset of type 2 diabetes through decreased glucose tolerance and insulin resistance. Uncontrolled diabetes can lead to serious health consequences such as impaired kidney function, blindness, stroke, myocardial infarction and lower limb amputation. Despite a variety of treatments currently available, cases of diabetes and resulting complications are on the rise. One promising new approach to diabetes focuses on modulating the gut microbiota with probiotics, prebiotics, synbiotics and fecal microbial transplantation. Differences in gut microbiota composition have been observed in preclinical animal models as well as patients with type 2 diabetes and complications such as diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, cerebrovascular disease, coronary heart disease and peripheral artery disease compared to healthy controls. Severity of gut microbiota dysbiosis was associated wi...
Polymers, 2021
Research regarding the use of biopolymers has been of great interest to scientists, the medical c... more Research regarding the use of biopolymers has been of great interest to scientists, the medical community, and the industry especially in recent years. Initially used for food applications, the special properties extended their use to the pharmaceutical and medical industries. The practical applications of natural drug encapsulation materials have emerged as a result of the benefits of the use of biopolymers as edible coatings and films in the food industry. This review highlights the use of polysaccharides in the pharmaceutical industries and as encapsulation materials for controlled drug delivery systems including probiotics, focusing on their development, various applications, and benefits. The paper provides evidence in support of research studying the use of biopolymers in the development of new drug delivery systems, explores the challenges and limitations in integrating polymer-derived materials with product delivery optimization, and examines the host biological/metabolic pa...
United Kingdom reported the emergence of a new and highly transmissible SARS-CoV-2 variant B.1.1.... more United Kingdom reported the emergence of a new and highly transmissible SARS-CoV-2 variant B.1.1.7. that rapidly spread to other contries. The impact of this new mutation that occurs in the S protein, on infectivity, virulence and current vaccine effectiveness is still under evaluation. We have identified the first cases of the B.1.1.7 variant in samples collected from Romanian patients, of which one was traced to the UK region where the new variant was originally sequenced. Mutations in the Nsp3 protein, N844S and D455N and L15F in Orf3a were also detected, indicating common ancestry with UK strains as well as remote connections with strains from Nagasaki, Japan. These results indicate, for the first time, the presence and characteristics of the new variant B.1.1.7 in Romania and underscore the need for increased genomic sequencing in confirmed COVID-19 patients.
Frontiers in Microbiology, 2021
Romania officially declared its first Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2... more Romania officially declared its first Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) case on February 26, 2020. The first and largest coronavirus disease 2019 (COVID-19) outbreak in Romania was recorded in Suceava, North-East region of the country, and originated at the Suceava regional county hospital. Following sheltering-in-place measures, infection rates decreased, only to rise again after relaxation of measures. This study describes the spread of SARS-CoV-2 in Suceava and other parts of Romania and analyses the mutations and their association with clinical manifestation of the disease during the period of COVID-19 outbreak. Sixty-two samples were sequenced via high-throughput platform and screened for variants. For selected mutations, putative biological significance was assessed, and their effects on disease severity. Phylogenetic analysis was conducted on Romanian genomes (n = 112) and on sequences originating from Europe, United Kingdom, Africa, Asia, South, an...
Biology, 2021
The ongoing COVID-19 pandemic follows an unpredictable evolution, driven by both host-related fac... more The ongoing COVID-19 pandemic follows an unpredictable evolution, driven by both host-related factors such as mobility, vaccination status, and comorbidities and by pathogen-related ones. The pathogenicity of its causative agent, SARS-CoV-2 virus, relates to the functions of the proteins synthesized intracellularly, as guided by viral RNA. These functions are constantly altered through mutations resulting in increased virulence, infectivity, and antibody-evasion abilities. Well-characterized mutations in the spike protein, such as D614G, N439K, Δ69–70, E484K, or N501Y, are currently defining specific variants; however, some less studied mutations outside the spike region, such as p. 3691 in NSP6, p. 9659 in ORF-10, 8782C > T in ORF-1ab, or 28144T > C in ORF-8, have been proposed for altering SARS-CoV-2 virulence and pathogenicity. Therefore, in this study, we focused on A105V mutation of SARS-CoV-2 ORF7a accessory protein, which has been associated with severe COVID-19 clinica...
Antibiotics, 2021
Periodontal disease is an oral infectious and inflammatory disease caused by microorganisms that ... more Periodontal disease is an oral infectious and inflammatory disease caused by microorganisms that determine the host-mediated destruction of soft and hard periodontal tissues, which ultimately leads to tooth loss. Periodontitis affects a large part of the population, with various degrees of severity. Treatment consists of etiologic therapy: the removal of biofilm through mechanical debridement plus microbial elimination by supplementary measures. Antibiotic administration, either systemically or through local delivery, has been shown to improve clinical outcomes after mechanical periodontal treatment. Clindamycin is a lincosamide with a broad spectrum, being active against aerobic, anaerobic, and β-lactamase-producing bacteria. This antibiotic offers several advantages and some disadvantages and has been used in periodontal treatment both systemically and locally with various degrees of success. Among the properties that recommend it for periodontal treatment is the bacteriostatic ef...
Journal of Clinical Medicine, 2021
Periodontitis is one of the most common immune-mediated inflammatory conditions resulting in prog... more Periodontitis is one of the most common immune-mediated inflammatory conditions resulting in progressive destruction of periodontium. Metalloproteinase-9 (MMP-9), an enzyme that is involved in the degradation of gelatin and collagen and present in the gingival crevicular fluid, is markedly increased in periodontitis. The aim of the study is to evaluate the effects of periodontal treatment either alone or in combination with orthodontic treatment on MMP-9 levels. In this study, 60 individuals were subjected to periodontal treatment (PD) or periodontal treatment combined with orthodontic treatment (POD). Both periodontal and periodontal plus orthodontic treatments significantly improved clinical parameters and lowered MMP-9 levels compared to control group. However, the combination of periodontal with orthodontic treatment further improved clinical parameters and enhanced the lowering effect on MMP-9 levels compared to periodontal or control groups alone. Finally, the degree of malocc...