Biology subjects

Rahman, S. M.

Publications and source records attributed to Rahman, S. M..

12 recordsLinked to original sources

bioRxiv2026

Schwann cell dysfunction contributes to diabetic wound pathology which is partially ameliorated by oncostatin M treatment

Chronic diabetic wounds represent a major clinical burden and are strongly associated with peripheral neuropathy, yet the contribution of nerve-associated Schwann cells to impaired healing remains poorly defined. Here, we investigated Schwann cell dynamics in cutaneous wound repair using the db/db model of type 2 diabetes. Full-thickness excisional wounds in db/db mice exhibited delayed closure, reduced dermal and epidermal thickness, and diminished cellular proliferation compared to non-diabetic controls. Diabetic wounds also demonstrated impaired re-innervation and a marked reduction in both total (S100{beta}+) and dedifferentiated (p75NTR+) Schwann cells, including decreased Schwann cell proliferation. These findings indicate that diabetes disrupts the injury-induced Schwann cell response that is essential for normal repair. Transcriptomic analyses revealed that injury-activated Schwann cells upregulate multiple trophic factors, including oncostatin M (OSM), while single-cell RNA sequencing demonstrated broad expression of OSM receptors (Osmr and Il6st) across wound-resident keratinocytes, fibroblasts, and vascular-associated cells, suggesting widespread responsiveness to OSM signalling during repair. Therapeutic administration of OSM to diabetic wounds significantly accelerated closure, reduced wound width and area, and increased dermal and epidermal thickness. Mechanistically, OSM enhanced epidermal proliferation, angiogenesis, and cutaneous axon regeneration. Collectively, these data identify Schwann cell dysfunction as a contributor to impaired diabetic wound healing and demonstrate that augmenting a Schwann cell-derived paracrine signal can partially rescue key reparative processes. Our findings support a regulatory role for Schwann cells in coordinating epithelial, vascular, and neural repair responses and highlight OSM signalling as a potential therapeutic strategy for chronic diabetic wounds.

cell biology↗

bioRxiv2024

Temporal and spatial distribution of microbial community in urban river in Dhaka

Buriganga River in central Bangladesh represents a complex ecosystem with extreme pollution and altered water quality. It is well known that microorganisms play a key role in regulating the function and health of aquatic ecosystems. Microbial activities also have a direct impact on biogeochemical cycling and degradation of pollutants. Despite numerous studies on the physicochemical parameters of the water quality of this central river, a comprehensive understanding of microbial diversity and the impact of waters physicochemical properties on bacterial community structure is not well documented. Therefore, the present investigation was done to elucidate the spatial and temporal shifts of microbial communities in the Buriganga River water in correlation to different physicochemical factors as well as heavy metal content. A total of 13 distinct sampling sites (from Amin Bazar Bridge to Postogola Cantonment B-C Friendship Bridge) encompassing a length of approximately 19 km along the rivers centre were selected to gather the sample seasonally during pre-monsoon, monsoon, post-monsoon, and winter. 16S rRNA gene-based metagenomics analysis revealed significant variation of bacterial diversity in winter rather than the rest of the three seasons with minimal variation suggesting stable geochemical cycles. Also, microbial diversity was higher at sampling points downstream compared to upstream along the river with overall dominance of Proteobacteria and Firmicutes. Physicochemical water quality parameters analysis identified Zn, TP (Total phosphate), BOD, and COD as key factors influencing bacterial community diversity and composition, although they were not the sole contributors. At the heavily polluted Lohar Bridge (10CS) site, significant nitrogen cycle disruption was evident. The high abundance of metal and antibiotic-resistant bacteria genera such as Pseudomonas, Ralstonia, and Acinetobacter at specific sampling positions indicated a relation between antibiotic and heavy metal pollution from adjacent hospitals and industrial effluent release points. The prevalence of metabolically unique bacteria such as Geobacter and Dehalococcoides, that are well known for utilizing specific heavy metals like iron and uranium as well as chlorinated compounds, might indicate the selective pressure of metal pollution from nearby working factories/industries. The investigation also identified potential pathogens like Arcobacter, Acinetobacter, and Pseudomonas, posing potential risks to both the environment and human health. Therefore, the Buriganga River belt serves as a potential hub for metal-antibiotic tolerant/resistant species with a direct influence on indigenous river-flowing communities correlating unique nutrient/geochemical cycling. The overall microbial community reflects unrestricted pollution in Buriganga central river aggravating water quality for regular use, indicating urgent intervention. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/625349v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@509d47org.highwire.dtl.DTLVardef@85d0b0org.highwire.dtl.DTLVardef@14813b5org.highwire.dtl.DTLVardef@105d1c1_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSignificant bacterial diversity was observed during winter compared to the other three seasons (Premonsoon, monsoon, and post monsoon). Zn, TP, BOD, and COD were found to be key factors influencing the diversity and composition of the bacterial community. Disruption of the nitrogen cycle was evident at the heavily polluted monitoring point. Potential pathogens were identified that may pose risks to both the environment and human health.

genomics↗

bioRxiv2024

Systemic CGRP and PACAP-38's Effects on Motion-Induced Nausea and Balance Behaviors in C57BL/6J Mice: A Comparison

Pituitary adenylate-cyclase-activating polypeptide (PACAP), particularly its dominant isoform PACAP-38, is implicated in migraine and represents a promising therapeutic target. We investigated if intraperitoneally delivered (IP) PACAP-38 impacts motion-induced nausea, postural sway, and imbalance in C57BL/6J wildtype mice using the motion-induced thermoregulation, center of pressure (CoP), rotarod, and balance beam assays. We also assessed systemic Calcitonin Gene-Related Peptides (CGRP) effects on these behaviors in parallel. Our findings indicate that IP PACAP-38 significantly disrupts motion-induced thermoregulation in mice, with notable blunting of tail vasodilation responses in both sexes. Additionally, PACAP-38 administration increased postural sway in female mice only and caused balance beam imbalances. Contrary to IP CGRP, IP PACAP-38 did not affect rotarod performance when mice were trained on a dowel with 1.5 cm radius. Our findings provide preclinical evidence supporting a potential role of PACAP-38 in vestibular migraine pathophysiology. Future research will explore if PACAP antagonism can protect against PACAP-38s effects on nausea and balance behaviors, relevant to treatment of vestibular migraine (VM), especially for patients unresponsive to triptans or CGRP-targeting therapies.

neuroscience↗

bioRxiv2024

Bioactivity Analysis of Secondary Metabolites from Actinomycetes' Isolated from Coastal Sediments

The rising threat of antibiotic resistance underscores the need for new antibiotics. Marine actinomycetes have emerged as promising sources of bioactive compounds. In this study, 22 isolates from marine sediments were morphologically identified, with nine confirmed as actinomycetes through 16S rRNA gene sequencing. Five strains- Streptomyces olivoverticillatus (T-2), Streptomyces cyaneus (T-4), Nocardiopsis synnemataformans (T-7), Streptomyces albogriseolus (T-8), and Streptomyces atrovirens (T-9)- exhibited significant antibacterial activity. Cultured in Starch Casein Broth, their metabolites were tested for antibacterial, antioxidant, anticoagulation, and anti-inflammatory activities. T-4 and T-8 demonstrated notable antimicrobial action, T-8 showing potent DPPH radical scavenging (372.09 {+/-} 11.05 {micro}g/mL). T-9 inhibited trypsin (IC50 435.12 {+/-} 15.88 {micro}g/mL) and had a prothrombin time of 12.08 {+/-} 1.46 minutes. T-8 enhanced RBC membrane stabilization (IC50 140.08 {+/-} 2.30 {micro}g/mL). These findings suggest that marine sediment-derived actinomycetes hold significant therapeutic potential and warrant further study.

microbiology↗

bioRxiv2023

Human RAMP1-overexpressing mice are resistant to migraine therapies for motion sensitivity: a mouse model of vestibular migraine

Both enhanced motion-induced nausea and increased static imbalance are observed symptoms in migraine and especially vestibular migraine (VM). Motion-induced nausea and static imbalance were investigated in a mouse model, nestin/hRAMP1, expressing elevated levels of human RAMP1 which enhances CGRP signaling in the nervous system, and compared to non-affected littermate controls. Behavioral surrogates such as the motion- induced thermoregulation and postural sway center of pressure (CoP) assays were used to assess motion sensitivity. Nausea readouts revealed that the nestin/hRAMP1 mouse exhibit an increased sensitivity to CGRPs effects at lower doses compared to unaffected controls. In addition, the nestin/hRAMP1 mice exhibit a higher dynamic range in postural sway than their wildtype counterparts, along with increased sway observed in nestin/hRAMP1 male mice that was not present in male unaffected controls. Results from migraine blocker experiments were challenging to interpret, but the data suggests that olcegepant is incapable of reversing CGRP-induced or endogenous alterations in the nestin/hRAMP1 mice, while rizatriptan was ineffective in both the nestin/hRAMP1 and control mice. The results indicate that overexpression of hRAMP1 leads to heightened endogenous CGRP signaling. Results also suggest that both olcegepant and rizatriptan are ineffective in reducing nausea and sway in this hypersensitive CGRP mouse model. This study suggests that the hypersensitive nestin/hRAMP1 mouse may serve as a model for difficult to treat cases of migraine that exhibit increased motion sensitivity.

neuroscience↗

bioRxiv2023

SARS-CoV-2 induces acute neurological signs while Calcitonin Gene-Related Peptide (CGRP) signaling blockade reduces interleukin 6 (IL-6) release and weight loss in mouse models

COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. However, neurological signs of SARS-CoV-2 infection have been hardly assessed in mouse models. Here, we infected two commonly used wildtype mice lines (C57BL/6 and 129S) with mouse-adapted SARS-CoV-2 and demonstrated neurological signs including motion- related dizziness. We then evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 CGRP-null mouse line with a mouse-adapted SARS- CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. First, we determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking CGRP. These findings suggest that migraine inhibitors such as those blocking CGRP signaling protect against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection, which may have repercussions for related pandemic and/or endemic coronaviruses. ImportanceCOVID-19 can cause neurological symptoms such as fever, headache, dizziness, and nausea. However, such neurological symptoms of SARS-CoV-2 infection have been hardly assessed in mouse models. Here, we first infected two commonly used wildtype mice lines (C57BL/6 and 129S) with mouse-adapted SARS-CoV-2 and demonstrated neurological signs including motion-related dizziness. Further, we showed that migraine treatment drug olcegepant could reduce long-term weight loss and IL-6 release associated with SARS-CoV-2 infection. These findings suggest that a migraine blocker can be protective for at least some acute SARS-CoV-2 infection signs and raise the possibility that it may also impact long-term outcomes of infection.

neuroscience↗

bioRxiv2023

Elucidating the role of muscarinic acetylcholine receptor (mAChR) signaling in efferent mediated responses of vestibular afferents in mammals

The peripheral vestibular system detects head position and movement through activation of vestibular hair cells (HCs) in vestibular end organs. HCs transmit this information to the CNS by way of primary vestibular afferent neurons. The CNS, in turn, modulates HCs and afferents via the efferent vestibular system (EVS) through activation of cholinergic signaling mechanisms. In mice, we previously demonstrated that activation of muscarinic acetylcholine receptors (mAChRs), during EVS stimulation, gives rise to a slow excitation that takes seconds to peak and tens of seconds to decay back to baseline. This slow excitation is mimicked by muscarine and ablated by the non-selective mAChR blockers scopolamine, atropine, and glycopyrrolate. While five distinct mAChRs (M1-M5) exist, the subtype(s) driving EVS-mediated slow excitation remain unidentified and details on how these mAChRs alter vestibular function is not well understood. The objective of this study is to characterize which mAChR subtypes drive the EVS-mediated slow excitation, and how their activation impacts vestibular physiology and behavior. In C57Bl/6J mice, M3mAChR antagonists were more potent at blocking slow excitation than M1mAChR antagonists, while M2/M4 blockers were ineffective. While unchanged in M2/M4mAChR double KO mice, EVS-mediated slow excitation in M3 mAChR-KO animals were reduced or absent in irregular afferents but appeared unchanged in regular afferents. In agreement, vestibular sensory-evoked potentials (VsEP), known to be predominantly generated from irregular afferents, were significantly less enhanced by mAChR activation in M3mAChR-KO mice compared to controls. Finally, M3mAChR-KO mice display distinct behavioral phenotypes in open field activity, and thermal profiles, and balance beam and forced swim test. M3mAChRs mediate efferent-mediated slow excitation in irregular afferents, while M1mAChRs may drive the same process in regular afferents.

neuroscience↗

bioRxiv2023

Both systemic Calcitonin Gene Related Peptide (CGRP) and a vestibular challenge promote anxiety-related behaviors and dynamic imbalance in mice

Motion-induced anxiety and agoraphobia are more frequent symptoms in patients with vestibular migraine than migraine without vertigo. The neuropeptide calcitonin gene-related peptide (CGRP) is a therapeutic target for migraine and vestibular migraine, but the link between motion hypersensitivity, anxiety, and CGRP is relatively unexplored, especially in preclinical mouse models. To further examine this link, we tested the effects of systemic CGRP and off-vertical axis rotation (OVAR) on elevated plus maze (EPM) and rotarod performance in male and female C57BL/6J mice. Rotarod ability was assessed using two different dowel diameters: mouse dowel (r = 1.5 cm) versus rat dowel (r = 3.5 cm). EPM results indicate CGRP increased anxiety indexes and time spent in the closed arms in females but not males, while OVAR increased anxiety indexes and time spent in the closed arms in both sexes. The combination of CGRP and OVAR elicited even greater anxiety-like behavior. On the rotarod, CGRP reduced performance in both sexes on a mouse dowel but had no effect on a rat dowel, whereas OVAR had a significant effect on the rat dowel. Rotarod performance is influenced by dowel diameter, with larger dowels presenting greater challenges on balance function. These results suggest that both CGRP and vestibular stimulation induce anxiety-like behavior and that CGRP affects dynamic balance function in mice depending on the type of challenge presented. Findings highlight the potential translation of anti-CGRP receptor signaling therapeutics for treating motion hypersensitivity and motion-induced anxiety that manifests in vestibular migraine. Significance statementAnxiety is very common in patients with dizziness and vestibular migraine (VM). Elevated CGRP levels have been linked to migraine symptoms of increased light and touch sensitivity in mice and humans and we wondered if a systemic injection of CGRP into mice would increase anxiety and imbalance; and if mice further exposed to a vestibular stimulus would have their anxiety measures sharpened. We observed a female preponderance in both CGRP and motion-induced anxiety-like behaviors, suggesting that the role of CGRP in migraines anxiety symptoms can be recapitulated in the mouse. Our findings suggest that CGRP signaling has a pertinent role in motion-induced anxiety and dynamic imbalance, and warrants the potential use of anti-CGRP therapies for the treatment of these symptoms.

neuroscience↗

bioRxiv2023

Age-Related Balance Problems in Mice Are Sharpened by the Loss of Calcitonin Gene-Related Peptide (CGRP) and a Vestibular Challenge

Aging impacts the vestibular system and contributes to imbalance. In fact, in the elderly balance deficits often precede changes in cognition. However, imbalance research is limited in assessing aging mouse models that are deficient in neuromodulators like Calcitonin Gene-Related Peptide (CGRP). We studied the loss of CGRP and its effects in the aging mouse, namely its effect on both static and dynamic imbalances. In addition, postural sway and rotarod testing were performed before and after a vestibular challenge (VC) in the 129S wildtype and the CGRP (-/-) null mice. Four age groups were tested that correspond to young adulthood, late adulthood, middle age, and senescence in humans. Our results suggest wildtype mice experience a decline in rotarod ability with increased age, while the CGRP (-/-) null mice perform poorly on rotarod early in life and do not improve. Our postural sway study suggests that a vestibular challenge can lead to significantly reduced CoP ellipse areas (freezing behaviors) in older mice, and this change occurs earlier in the CGRP (-/-) null mouse. These results indicate that CGRP is an important component of static and dynamic balance; and that the loss of CGRP can contribute to balance complications that may compound with aging.

neuroscience↗

bioRxiv2022

Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonism Reduces Motion Sickness Indicators in Mouse Models of Vestibular Migraine

Structured AbstractO_ST_ABSBackgroundC_ST_ABSMigraine and especially vestibular migraine are associated with enhanced motion sickness and motion-induced nausea. Murine models of migraine have used injections of Calcitonin Gene-Related Peptide (CGRP) or other migraine triggers [i.e., sodium nitroprusside (SNP)] to induce migraine sensitivities to touch and light. Yet, there is limited research on whether these triggers increase motion-induced nausea, and if migraine blockers can reduce these migraine symptoms. We hypothesized that systemic delivery of CGRP or SNP will increase motion sickness susceptibility and motion-induced nausea in mouse models, and that migraine blockers can block these changes induced by systemically delivered CGRP or SNP. MethodsWe investigated two measures of motion sickness assessment [motion sickness index (MSI) scoring and motion-induced thermoregulation] after intraperitoneal injections of either CGRP or SNP in C57B6/J mice. The drugs olcegepant, sumatriptan, and rizatriptan were used to assess the efficacy of migraine blockers. ResultsMSI measures were confounded by CGRPs effect on gastric distress. However, analysis of tail vasodilations as a surrogate for motion-induced nausea was robust for both migraine triggers. Only olcegepant treatment rescued tail vasodilations. ConclusionThese preclinical findings support the use of small molecule CGRP receptor antagonists for the treatment of motion-induced nausea of migraine, and show that triptan therapeutics are ineffective against motion-induced nausea of migraine.

neuroscience↗

bioRxiv2022

Role of Calcitonin Gene-Related Peptide (CGRP) in Auditory, Static, and Dynamic Imbalance Behaviors: Implications for Vestibular Migraine

Migraine is a severe and chronic neurological disorder that affects [~]18% of people worldwide, the majority being female (3:1). It is characterized by recurrent, debilitating headaches and heightened sensory sensitivities. People with migraine may develop vestibular migraine (VM), characterized by a heightened motion sensitivity and preponderance for spontaneous vertigo attacks and balance problems such as postural instability. Calcitonin gene-related peptide (CGRP) is implicated in migraine and is believed to act on brain meninges or in subcortical central nervous system (CNS) structures, and CGRP-based antagonists have shown efficacy for migraine treatment. CGRP also signals at efferent synapses of the cochlea and vestibular end organs, but it is unclear if exogenous CGRP can modulate inner ear function at the end organ level and cause heightened behavioral responses consistent with VM. We tested if intraperitoneally (IP) delivered CGRP to wildtype mice can modulate end organ potentials to sound [via auditory brainstem responses (ABRs)] and jerk stimuli [via vestibular sensory evoked potentials (VsEPs)]. We also assessed behavioral measures of phonophobia [acoustic startle reflex (ASR)] and static imbalance [postural sway-center of pressure (CoP)] after IP CGRP, and observed female mice exhibited heightened sensitivities to IP CGRP in all assays. Male mice showed similar auditory sensitivity and end organ effects to CGRP, but systemic CGRP did not modify male postural sway as it did in females. In conclusion, we show that intraperitoneally delivered CGRP affects ABRs and VsEPs, and elicits behaviors suggestive of auditory hypersensitivity and postural instability in mice related to the phonophobia and postural instability seen in VM patients. Significance StatementCalcitonin Gene-Related Peptide (CGRP) has been implicated in migraine, and CGRP-based therapeutics have shown efficacy in the treatment of migraine headaches. CGRP is also present in efferent synapses of the inner ear, so we questioned if increases in systemic CGRP can act directly on inner ear end organs and modify corresponding behavioral responses. In this study, we determined systemic CGRP changes cochlear and vestibular end organ potentials and produces migraine behaviors similar to phonophobia and postural control deficits. Peripheral changes in auditory and vestibular compound action potentials following systemic CGRP administration suggest CGRP can act directly on the inner ear, which provides one site of action for CGRPs involvement in hypersensitivity to sound and movement in migraine.

neuroscience↗

bioRxiv2020

Machine Learning-based Biomarkers Identification and Validation from Toxicogenomics - Bridging to Regulatory Relevant Phenotypic Endpoints

High-throughput in vitro assays and AOP-based approach is promising for the assessment of health and ecotoxicological risks from exposure to pollutants and their mixtures. However, one of the major challenges in realization and implementations of the Tox21 vision is the urgent need to establish quantitative link between in-vitro assay molecular endpoint and in-vivo phenotypic toxicity endpoint. Here, we demonstrated that, using time series toxicomics in-vitro assay along with machine learning-based feature selection (MRMR) and classification method (SVM), an "optimal" number of biomarkers with minimum redundancy can be identified for prediction of phenotypic endpoints with good accuracy. We included two case studies for in-vivo carcinogenicity and Ames genotoxicity prediction with 20 selected chemicals including model genotoxic chemicals and negative controls, respectively, using an in-vitro toxicogenomic assay that captures real-time proteomic response data of 38 GFP-fused proteins of S. cerevisiae strains covering biomarkers indicative of all known DNA damage and repair pathways in yeast. The results suggested that, employing the adverse outcome pathway (AOP) concept, molecular endpoints based on a relatively small number of properly selected biomarker-ensemble involved in the conserved DNA-damage and repair pathways among eukaryotes, were able to predict both in-vivo carcinogenicity in rats and Ames genotoxicity endpoints. The specific biomarkers identified are different for the two different phenotypic genotoxicity assays. The top-ranked five biomarkers for the in-vivo carcinogenicity prediction mainly focused on double strand break repair and DNA recombination, whereas the selected top-ranked biomarkers for Ames genotoxicity prediction are associated with base- and nucleotide-excision repair. Current toxicomics approach still mostly rely on large number of redundant markers without pre-selection or ranking, therefore, selection of relevant biomarkers with minimal redundancy would reduce the number of markers to be monitored and reduce the cost, time, and complexity of the toxicity screening and risk monitoring. The method developed in this study will help to fill in the knowledge gap in phenotypic anchoring and predictive toxicology, and contribute to the progress in the implementation of tox 21 vision for environmental and health applications. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/423486v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@11bc876org.highwire.dtl.DTLVardef@105ebc2org.highwire.dtl.DTLVardef@1b91a63org.highwire.dtl.DTLVardef@1738486_HPS_FORMAT_FIGEXP M_FIG TOC Art C_FIG

pharmacology and toxicology↗