Md. Mahbubur Rahman | Gacheon University (original) (raw)

Papers by Md. Mahbubur Rahman

Frontiers, 2024

The transient receptor potential ankyrin 1 (TRPA1) channel plays a pivotal role in the respirator... more The transient receptor potential ankyrin 1 (TRPA1) channel plays a pivotal role in the respiratory and gastrointestinal tracts. Within the respiratory system, TRPA1 exhibits diverse distribution patterns across key cell types, including epithelial cells, sensory nerves, and immune cells. Its activation serves as a frontline sensor for inhaled irritants, triggering immediate protective responses, and influencing airway integrity. Furthermore, TRPA1 has been implicated in airway tissue injury, inflammation, and the transition of fibroblasts, thereby posing challenges in conditions, such as severe asthma and fibrosis. In sensory nerves, TRPA1 contributes to nociception, the cough reflex, and bronchoconstriction, highlighting its role in both immediate defense mechanisms and long-term respiratory reflex arcs. In immune cells, TRPA1 may modulate the release of pro-inflammatory mediators, shaping the overall inflammatory landscape. In the gastrointestinal tract, the dynamic expression of TRPA1 in enteric neurons, epithelial cells, and immune cells underscores its multifaceted involvement. It plays a crucial role in gut motility, visceral pain perception, and mucosal defense mechanisms. Dysregulation of TRPA1 in both tracts is associated with various disorders such as asthma, Chronic Obstructive Pulmonary Disease, Irritable Bowel Syndrome, and Inflammatory Bowel Disease. This review emphasizes the potential of TRPA1 as a therapeutic target and discusses the efficacy of TRPA1 antagonists in preclinical studies and their promise for addressing respiratory and gastrointestinal conditions. Understanding the intricate interactions and cross-talk of TRPA1 across different cell types provides insight into its versatile role in maintaining homeostasis in vital physiological systems, offering a foundation for targeted therapeutic interventions.

Elsevier, 2024

Neuropathic pain, a common symptom of several disorders, exerts a substantial socioeconomic burde... more Neuropathic pain, a common symptom of several disorders, exerts a substantial socioeconomic burden worldwide. Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel predominantly expressed in nociceptive neurons, plays a pivotal role in nociception, by detecting various endogenous and exogenous stimuli, including heat, pro-inflammatory mediators, and physical stressors. Dysregulation of TRPV1 signaling further contributes to the pathophysiology of neuropathic pain. Therefore, targeting TRPV1 is a promising strategy for developing novel analgesics with improved efficacy and safety profiles. Several pharmacological approaches to modulate TRPV1 activity, including agonists, antagonists, and biological TRPV1 RNA interference (RNAi, small interfering RNA [siRNA]) have been explored. Despite preclinical success, the clinical translation of TRPV1-targeted therapies has encountered challenges, including hyperthermia, hypothermia, pungency, and desensitization. Nevertheless, ongoing research efforts aim to refine TRPV1-targeted interventions through structural modifications, development of selective modulators, and discovery of natural, peptide-based drug candidates. Herein, we provide guidance for researchers and clinicians involved in the development of new interventions specifically targeting TRPV1 by reviewing the existing literature and highlighting current research activities. This study further discusses potential future research endeavors for enhancing the efficacy, safety, and tolerability of TRPV1 candidates, and thereby facilitates the translation of these discoveries into effective clinical interventions to alleviate neuropathic pain disorders.

Diosgenin is a botanical steroidal saponin with immunomodulatory, anti-inflammatory, anti-oxidati... more Diosgenin is a botanical steroidal saponin with immunomodulatory, anti-inflammatory, anti-oxidative, anti-thrombotic, anti-apoptotic, anti-depressant, and anti-nociceptive effects. However, the effects of diosgenin on anti-nociception are unclear. Transient receptor potential vanilloid 1 (TRPV1) plays an important role in nociception. Therefore, we investigated whether TRPV1 antagonism mediates the anti-nociceptive effects of diosgenin. In vivo mouse experiments were performed to examine nociception-related behavior, while in vitro experiments were performed to examine calcium currents in dorsal root ganglion (DRG) and Chinese hamster ovary (CHO) cells. The duration of capsaicin-induced licking (pain behavior) was significantly reduced following oral and intraplantar administration of diosgenin, approaching levels observed in mice treated with the TRPV1 antagonist N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl) tetrahydropyrazine-1(2H)carbox-amide. Additionally, oral administration of diosgenin blocked capsaicin-induced thermal hyperalgesia. Further, diosgenin reduced capsaicin-induced Ca 2+ currents in a dose-dependent manner in both DRG and CHO cells. Oral administration of diosgenin also improved thermal and mechanical hyperalgesia in the sciatic nerve constriction injury-induced chronic pain model by reducing the expression of TRPV1 and inflammatory cytokines in DRG cells. Collectively, our results suggest that diosgenin exerts analgesic effects via antagonism of TRPV1 and suppression of inflammation in the DRG in a mouse model of neuropathic pain.

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Gamma-aminobutyric acid (GABA) neuronal system-related transcription factors (TFs) play a critica... more Gamma-aminobutyric acid (GABA) neuronal system-related transcription factors (TFs) play a critical role in GABA production, and GABA modulates diabetic neuropathic pain (DNP). The present study investigated the therapeutic effects of intrathecal delivery of two TFs achaete-scute homolog 1 (Ascl1) and LIM homeobox protein 6 (Lhx6) in a mouse model of DNP and elucidated their underlying mechanisms. GABA-related specific TFs, including Ascl1, Lhx6, distal-less homeobox 1, distal-less homeobox 5, the Nkx2.1 homeobox gene, and the Nkx2.2 homeobox gene, were investigated under normal and diabetic conditions. Among these, the expression of Ascl1 and Lhx6 was significantly downregulated in mice with diabetes. Therefore, a single intrathecal injection of combined lenti-Ascl1/Lhx6 was performed. Intrathecal delivery of lenti-Ascl1/Lhx6 significantly relieved mechanical allodynia and heat hyperalgesia in mice with DNP. Ascl1/Lhx6 delivery also reduced microglial activation, decreased the levels of pro-inflammatory cytokines including tumor necrosis factor-α and interleukin (IL)-1β, increased the levels of anti-inflammatory cytokines including IL-4, IL-10, and IL-13, and reduced the activation of p38, c-Jun N-terminal kinase, and NF-κB in the spinal cord of mice with DNP, thereby reducing DNP. The results of this study suggest that intrathecal Ascl1/Lhx6 delivery attenuates DNP via upregulating spinal GABA neuronal function and inducing anti-inflammatory effects.

This article is protected by copyright. All rights reserved. 2 This study aimed to investigate th... more This article is protected by copyright. All rights reserved. 2 This study aimed to investigate the bone regeneration effect of bovine hydroxyapatite-processed biomaterials Bone-XB and S1-XB in a beagle mandibular defect model. A total of four saddle-type critical sizes (15 mm × 10 mm) bone defects were created in each dog: two defects in the left mandible and two defects in the right mandible. The defect control (DC) group was kept unfilled, and the other three defects were filled with three different biomaterials as follows: positive control Bio-Oss ® (Bio-Oss group), Bone-XB (XB group), and S1-XB (S1-XB group). Bone regeneration was evaluated by radiography, micro-computed tomography, and histological analysis. we revealed that Bone-XB and S1-XB significantly increased newly formed bone, defect filling percentage, and bone healing score compared to the DC group, which was confirmed by bone microstructure augmentation (bone volume/total volume, trabecular number, and trabecular thickness). Interestingly, no significant differences were observed between the Bone-XB, S1-XB, and Bio-Oss groups. We suggest that Bone-XB or S1-XB stimulates bone regeneration demonstrated by the increase in newly formed bone and bone microstructure, thereby improving bone defect filling, which was equivalent to the Bio-Oss ®. Therefore, bovine hydroxyapatite-processed Bone-XB or S1-XB could be considered effective biomaterials for correcting critical-size bone defects or fractures.

Objective: The objective of this retrospective study was to evaluate the preoperative clinical ch... more Objective: The objective of this retrospective study was to evaluate the preoperative clinical characteristics to predict postoperative neurologic recovery in dogs with intervertebral herniated disk disease (IVDD). Materials and Methods: The dogs were classified according to postoperative neurologic recovery from clinical history of the hospital e-book. Excellent when dogs (n=13) were neurologically normal; good (n=8) when postoperative neurologic grade was improved from preoperative condition had improved sufficiently to require no or minor therapy after discharge; fair (n=4) is considered when postoperative neurologic status was unchanged from preoperative condition and poor (n=5) when major postoperative complication developed as a consequences neurologic grade had worsened at discharge than their preoperative score or the patient died. The evaluated preoperative clinical characteristics in all groups are breed, age, sex, duration of clinical sings appearance (DCSA), preoperative neurologic grading system (PNGS), compression rate (pre and postoperative) in MRI and CT scan, housefield unit (HU), type of IVDD and surgical procedures, and compared with excellent group. Results: no definitive relationship was found between the clinical characteristics and neurologic recovery, except, DCSA and preclinical neurologic pathological condition. The DCSA were 73.54±15.00, 117.63±31.58, 171.25±99.56 and 175.00±94.83 (P<0.05), respectively. The PNGS were 3±0, 3±0, 4±0 and 4±0 (P<0.01), respectively. Conclusion: Finally based on this clinical study, it is recommended that postoperative recovery greatly depends on DCSA and PNGS in IVDD dogs.

Objective: Bilateral ureteral calculi, hydronephrosis, pyometra, pyocolpos, vestibulovaginal sten... more Objective: Bilateral ureteral calculi, hydronephrosis, pyometra, pyocolpos, vestibulovaginal steno-sis, and imperforate hymen in a dog are uncommon and can be difficult to diagnose. The aim of this article is to report diagnostic challenges and successful surgical treatment of this rare event and the long-term outcomes. Materials and methods: A 5-year-old, spayed (partial ovariohysterectomy) female dog was primarily diagnosed with bilateral hydronephrosis and ureter obstruction due to urolithiasis along with pyometra. The urolith was removed carefully by the right-side ureterectomy, an appropriate ureteral stent was inserted from the bladder to the right kidney, and then, a vasectomy and hysterectomy were performed. The dog improved and was discharged. However, 50 days after surgery , pyocolpos due to imperforate hymen and vestibulovaginal stenosis were diagnosed and surgically corrected, and the ureteral stent was removed because the ureter had completely healed. Results: During the first admission, serum biochemistry results revealed the increased blood urea nitrogen (5.9 mg/dl), creatinine (116.2 mg/dl), amylase (1,345 U/l), and lipase (141 U/l) values. After surgical correction, all parameters returned to normal. However, 50 days after surgery, the C-reactive protein concentration (143 mg/l) and white blood cell level increased (18.4 × 10 9 /l). After a second surgical correction, the dog recovered fully within 10 days, and no postoperative complications were observed during the follow-up of 6 months. Conclusion: This report provides diagnostic assistance and surgical treatment options for a complex urogenital case. Careful examination during puberty is recommended to prevent the associated complications of this disorder. ARTICLE HISTORY

Objective: In Korea, small dogs are more common than large breeds. This study was performed to me... more Objective: In Korea, small dogs are more common than large breeds. This study was performed to measure the influence of body weight, sex, breed, age, and cranial cruciate ligament rupture (RCCL) on the tibial plateau angle (TPA) in small-breed dogs. Materials and methods: A total of 274 dogs (221 normal dogs and 53 RCCL dogs) were selected for this study based on medical records. The TPA was measured from stifle joint radiographs. The dogs were divided according to body weight, sex (male and female; normal and neutered), age, breed, and RCCL, and the TPAs of the dogs were compared. Results: In general, the TPAs of male dogs were significantly (p < 0.05) higher than those of female dogs, and those of healthy neutered dogs were higher than those of healthy intact dogs. The TPA had a tendency to increase along with the animal's age but was not significantly different among the four age groups. In general, the TPA of RCCL dogs was 27.12° ± 0.62°, which was significantly higher (p < 0.001) than that of normal dogs (20.21° ± 0.32°), indicating that an increased TPA is associated with a higher risk for RCCL. Similar results were also observed among dogs with similar body weights, breeds, and ages for male and female RCCL dogs. Conclusion: This study suggested that the sex and neutering status of dogs could affect the TPA. This study also confirmed the use of TPA in the veterinary clinic as a possible indicator of RCCL, as the TPA is higher in RCCL dogs than in normal dogs. ARTICLE HISTORY

Elsevier, 2020

Introduction: In recent decades, fine-dust particulate matter (FM) has become a potential health ... more Introduction: In recent decades, fine-dust particulate matter (FM) has become a potential health hazard, causing
various pathological respiratory disorders around the world. Inflammation induced by FM is regarded as a major
cause of respiratory disorder in humans. The purpose of this study was to evaluate the therapeutic efficacy of
Shibashin Misena®, a functional food composed of various bioactive ingredients, on FM-induced respiratory
disorders in mice.
Materials and methods: Briefly, 40 mice were divided equally into four groups: normal controls (NC); FM-induced
control group (FC); FM group treated with Shibashin Misena® 0.1 mL/head/day (FM0.1); FM group treated with
Shibashin Misena® 0.2 mL/head/day (FM0.2).
Results: FM significantly induced TNF-α, IL-17A, IL-1β, and TGF-β in bronchoalveolar lavage fluid (BALF)
collected from the FM mice. Compared with FC, Shibashin Misena® decreased TNF-α, IL-17A, and IL-1β levels in
BALF, and histopathologic evaluations revealed that Shibashin Misena® treatment significantly reduced inflammatory-
cell infiltration and fibrosis related collagen deposition in lung tissue.
Conclusion: This study demonstrated that Shibashin Misena® decreased FM-induced inflammation and fibrosis in
lung tissue. Thus, Shibashin Misena® could be an effective supplement to prevent or improve FM-induced pulmonary
disorders.

Citation: Jeong IS, Rahman MM, Choi GC, Seo BS, Lee GJ, Kim S, Kim NS (2019): A retrospective stu... more Citation: Jeong IS, Rahman MM, Choi GC, Seo BS, Lee GJ, Kim S, Kim NS (2019): A retrospective study of canine cervi-cal disk herniation and beneficial effects of rehabilitation therapy after ventral slot decompression. Veterinarni medicina 64, 251-259. Abstract: The objective of this study was to evaluate the clinical outcome of ventral slot decompression and rehabilitation therapy in dogs with cervical intervertebral disc herniation (IVDH). Surgical decompression was performed in dogs with IVDH using the ventral slot procedure. After surgery, physiotherapeutic rehabilitation consisted of a combination of electrotherapy, infrared therapy and mechanical massage; treadmill exercise was started when the animal could stand up. A total of 58 dogs were selected from the hospital and included in two groups: rehabilitated group (RG, n = 34) and non-rehabilitated group (NRG, n = 24). Dogs of each group were subdivided into five groups based on a pre-operative clinical grading system. Grade 1 designated spinal pain only, grade 2 designated ambulatory paraparesis, grade 3 designated non-ambulatory paraparesis, grade 4 designated paraplegia with deep-pain perception intact and grade 5 designated paraplegia without deep-pain perception. Post-operative changes of both groups were evaluated and compared, including time until unassisted standing and walking after surgery and the success rate. Overall, 79.41% (27/34) of dogs had a successful neurologic outcome in the RG group, which was significantly (P < 0.05) higher than the NRG group 62.50% (15/24). Interestingly, the success rate differed when the preoperative grading system was considered. The success rates of grades 1, 2, 3, 4 and 5 were 100% (9/9), 100% (7/7), 75% (3/4), 53.85% (7/13) and 100% (1/1), respectively, in the rehabilitated groups, whereas in the non-rehabilitated groups success rates were 100% (5/5), 83.33% (5/6), 60.00% (3/5), 28.57% (2/7) and 0% (0/1), respectively. The differences in success rates between the two groups according to grading were 0, 16.67, 15, 25.57 and 100%, respectively. The proposed rehabilitation therapy after surgical decompression of cervical IVDH can improve the success rate when the preoperative pathological condition is severe.

Paclitaxel is used in the treatment of cancer especially in breast, stomach and ovarian cancer. H... more Paclitaxel is used in the treatment of cancer especially in breast, stomach and ovarian cancer. However, peripheral neuropathic pain (PNP) induction is the most common devastating side effect of paclitaxel treatment. The objective of this study was to evaluate the PNP related behavioral changes in rats following oral administration of a novel oral paclitaxel formulation DHP107 (Liporaxel) in comparison with another popular intravenous paclitaxel preparation (Taxol). The rats were equally divided in to three groups namely, NC group (normal control): was treated with saline in a matched volume, LPX group (Liporaxel were administered orally) and TAX group (Taxol was administered intravenously). Less pain like behaviors were observed in LPX group in comparison with TAX group evidenced by significant higher level of hot plate paw withdrawal threshold (PWT), von Frey filament PWT and mechanical PWT than TAX group. Reduced lipid peroxidation and elevated antioxidant activities in serum, dorsal root ganglion (DRG) and sciatic nerve (SN) in LPX group than TAX group. In addition, cell apoptosis and expression of pain and neuropathy related proteins activation in LPX group was found lowered and myelin sheath thickness was higher in DRG and SN but not significantly different from the TAX group. Therefore, oral DHP107 could be a promising chemotherapeutic agent due to inducing less PNP.

Frontiers, 2024

Elsevier, 2024

Elsevier, 2020