BackgroundGalectin-3 (Gal-3), a β-galactoside-binding lectin of the chimera subtype, is markedly upregulated in activated microglia in Alzheimer's disease (AD), where it amplifiesTLR4–NF-κB neuroinflammatory signalling through a self-sustaining positive feedbackloop. No reports have been made on the systematic computational evaluation of Plukenetia volubilis seed oil phytochemicals as inhibitors of the Gal-3 carbohydrate recognition domain (CRD).MethodsFifteen phytochemicals from P. volubilis were selected through literature-guided chemical diversity analysis. Molecular docking against the Gal-3 CRD (PDB: 7CXD; 1.45 Å) was performed using Schrödinger Maestro Glide SP/XP with MM-GBSA refinement. Physicochemical descriptors were computed using RDKit (v2023.09); ADME was profiled via SwissADME and ADMET-ai. Blood–brain barrier (BBB) permeability was assessed by a four-model ML consensus: QikProp, SwissADME BOILED-Egg, ChemBERTa-BBB transformer (AUC = 0.93 on B3DB), and DeepPred-BBB deep neural network (sensitivity = 0.93). Hierarchical clustering and PCA characterized compound chemical space.ResultsProtocol validation: RMSD = 1.74 Å. Apigenin (GlideScore: − −1

Brain-derived neurotrophic factor (BDNF) is classically recognized for its role in neuronal survival and synaptic plasticity; however, increasing evidence highlights its important regulatory functions within the respiratory system. In the lung, BDNF and its receptors, particularly tropomyosin receptor kinase B (TrkB), are expressed by airway epithelial cells, airway smooth muscle, immune cells, fibroblasts, and neurons, positioning BDNF as a central mediator of neuroimmune-epithelial crosstalk. Activation of BDNF-TrkB signaling engages multiple intracellular pathways, including phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), phospholipase C-γ (PLCγ), and small GTPase-dependent cascades, thereby regulating epithelial repair, airway contractility, inflammation, fibrosis, and neural plasticity. Dysregulation of this signaling axis has been implicated in the pathogenesis of major respiratory diseases. In asthma, excessive BDNF activity contributes to airway hyperresponsiveness and remodeling, whereas in chronic obstructive pulmonary disease reduced BDNF signaling is associated with impaired epithelial regeneration. In idiopathic pulmonary fibrosis, BDNF promotes fibroblast activation and extracellular matrix deposition, while in acute lung injury and acute respiratory distress syndrome its effects appear context dependent, supporting epithelial survival during acute injury but exacerbating pathology when persistently elevated. Emerging evidence further implicates epigenetic mechanisms, microRNAs, and cellular heterogeneity revealed by single-cell transcriptomics in shaping disease-specific BDNF responses. Collectively, these findings identify BDNF as a context-dependent regulator of pulmonary homeostasis and disease. Targeted modulation of BDNF-TrkB signaling therefore represents a promising, yet complex, therapeutic avenue for chronic and acute respiratory disorders.

Oxidative stress is a central mechanism in metabolic, cardiovascular, and neurodegenerative diseases, contributing to inflammation, mitochondrial dysfunction, and apoptosis. Consequently, redox-modulating therapies are increasingly explored as potential therapeutic strategies. This review evaluates the mechanistic basis, experimental evidence, and clinical applicability of hydrogen-rich water (HRW) in oxidative stress-related diseases. A structured literature search identified mechanistic, preclinical, and clinical studies investigating HRW or molecular hydrogen (H2) on oxidative stress, inflammation, mitochondrial regulation, and disease-related outcomes. Due to substantial methodological heterogeneity, findings were synthesized qualitatively. HRW has been proposed to selectively neutralize highly reactive species such as hydroxyl radicals (•OH) and peroxynitrite (ONOO-) while preserving physiological reactive oxygen species signalling. Mechanistic studies demonstrate activation of nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathways, suppression of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) inflammatory cascades, modulation of JAK/STAT signalling, preservation of mitochondrial bioenergetics, and enhancement of autophagic regulation. Preclinical and clinical studies report improvements in glycaemic control, endothelial function, cardiometabolic health, neuroprotection, exercise performance, and treatment-related fatigue. Despite an excellent safety profile, standardization of HRW preparation and large multicentre randomized controlled trials (RCTs) remain necessary to establish clinical efficacy and translational potential.

A notable number of patients with diabetes suffer from painful diabetic neuropathy (PDN), which is a debilitating complication of diabetes mellitus. Prolonged hyperglycaemia and metabolic dysregulation lead to PDN, a condition characterised by chronic pain, sensory dysfunction, and reduced quality of life. Although various treatment options are available, clinical management is challenging due to the complex and multifactorial nature of PDN pathophysiology. N-methyl-D-aspartate receptors (NMDARs), particularly the NR2B subtype (NMDAR-2B), have emerged as a key player in the pathophysiology of chronic pain states, including PDN. This review highlights the mechanistic NMDAR-2B involvement in the pathophysiology of PDN, focusing on its upregulation role in pain-processing regions, interaction with inflammatory mediators, glia-derived mediators, and oxidative stress mechanisms. Advancements in targeting NMDAR-2B as a mechanistically driven approach to PDN management also offer potential in enhancing the therapeutic efficacy of NMDAR-2B. Consequently, this review provides a novel perspective on understanding the role of NMDAR-2B in PDN for the future development of effective treatment strategies for managing the condition.

This study investigated the effects of minocycline on proinflammatory cytokines, oxidative stress marker levels in the spinal cord and sciatic nerve morphology in Type 2 diabetic (T2DM) neuropathy rats. Male Sprague Dawley rats were randomly assigned to six groups (n = 14 per groups): Control (C), T2DM control (STZ), T2DM treated with minocycline 40 mg/kg (STZ + M40) and 80 mg/kg (STZ + M80), T2DM treated with gabapentin (STZ + G10) and non-painful T2DM neuropathy (NPDN). T2DM was induced in obese rats using a combination of high fat diet (HFD) and low-dose streptozotocin (STZ) (40 mg/kg) injection. Then, the neuropathic pain behaviour, body weight and blood biochemical analysis were performed. Rats were sacrificed and the spinal cord and sciatic nerve were collected for ELISA and histology examination. T2DM rat groups were significantly increased body weight after 6 weeks but significantly reduced from 8 until 9 weeks compared to control group (p < 0.05). The fasting blood glucose (FBG) level in all T2DM groups were significantly higher on day 3, day 14, and day 22 compared to control group (p < 0.05) consistent with HbA1c levels. T2DM groups also significantly increased MDA, TNF-α, IL-1β and C-Reactive Protein (CRP) but decreased SOD and Catalase levels in the spinal cord compared to control group (p < 0.05). T2DM groups also showed significant abnormal morphology changes in the sciatic nerve compared to control group (p < 0.05). Minocycline dependent on doses and gabapentin in T2DM rat significantly alleviated all these effects. These findings suggest the neuroprotective effects of minocycline on T2DM neuropathy.

Minocycline has been shown to ameliorate neuroinflammation that was encountered in many neurodegenerative diseases. This study aims to investigate the expression of inflammatory mediators in the rat medial prefrontal cortex (mPFC) after minocycline treatment in a lipopolysaccharide (LPS)- induced neuroinflammation rat model. Adult male Sprague Dawley (SD) rats (N = 50) were divided into 5 groups: (1) control, (2) LPS (5 mg/kg), (3) LPS + minocycline (25 mg/kg), (4) LPS + minocycline (50 mg/kg) and (5) LPS + memantine (10 mg/kg). Intraperitoneal minocycline and memantine were given daily for 14 days, while LPS injection was given once on the 5th day. Western blot and immunohistochemistry were used to assess density and expression of toll-like receptor-4 (TLR-4), nuclear factor kappa-B (NF-kB), tumor necrosis factor (TNF)-α and cyclooxygenase (COX)-2 in the medial prefrontal cortex (mPFC) of rats. Findings displayed that minocycline significantly decreased expression and density of TLR-4, NF-kB, TNF-α and COX-2 proteins that were comparable to memantine in mPFC of SD rat injected with single intraperitoneal LPS. Interestingly, the anti-inflammatory effects of minocycline 50 mg/kg were significantly more than minocycline 25 mg/kg. This study suggested that minocycline can modulate LPS-induced neuroinflammation in dose-dependent manner in the mPFC area. Thus, it is suggested that minocycline can be used as potential preventive-therapeutic drug for neuroinflammatory diseases such as depression and anxiety.

Chronic pain is a significant and global healthcare issue that hugely implies the quality of life and productivity of the affected individuals. It is challenging to treat and thus necessitates a deeper understanding of its underlying pathomechanisms to develop targeted interventions. Serotonin is one of the essential neurotransmitters involved in the propagation of pain signals through both ascending and descending pathways, acting via various receptor subtypes, including the 5-hydroxytryptamine receptor-6 (5-HT6R). Recent studies have shed light on the involvement of 5-HT6R in the pathophysiology of chronic pain. This review aimed to uncover the emerging roles of 5-HT6R in chronic pain research by focusing on its functions in pain modulation, neuronal excitability, and pain processing. Although 5-HT6R has been recently discovered, previous studies have revealed its therapeutic effects in modulating chronic pain. Understanding the precise mechanism underlying the 5-HT6R may offer new avenues for future strategies of chronic pain management and indirectly improve the individual’s quality of life. However, further research is warranted to elucidate the intricate interplay between 5-HT6R and other pain modulatory pathways, paving the way for more effective and tailored therapeutic strategies for chronic pain.

Background/Objectives:Massage therapy has been shown to alleviate stress and improve well-being, making it a promising intervention for healthcare professionals who often face high levels of job-related stress. This study investigated the effects of automated massage chair therapy on negative emotional states, musculoskeletal pain, and biochemical markers in healthcare professionals. Methods:Twenty-four healthcare professionals with moderate levels of depression, anxiety, and stress were randomly assigned to either an automated massage chair group or a progressive muscle relaxation (PMR) group. Each group received 15-min sessions, three times per week for 4 weeks, totaling 12 sessions. The depression, anxiety, and stress scale-21 items (DASS-21), the visual analog scale (VAS) for pain, and blood biomarkers [brain-derived neurotrophic factor (BDNF), cortisol, beta-endorphin, superoxide dismutase 1 (SOD1), endothelial nitric oxide synthase (eNOS), and myeloperoxidase (MPO)] were measured at baseline, after six sessions, and after 12 sessions. Results:The massage chair group showed significant reductions in depression scores at 6 sessions (Z = -2.043, p = 0.041), and in stress scores at 6 (Z = -2.499, p = 0.012) and 12 sessions (Z = -2.326, p = 0.020). Calf pain scores improved significantly at 12 sessions (right calf: Z = -2.677, p = 0.007; left calf: Z = -2.253, p = 0.024), and lower back pain reduced at both 6 (Z = -2.275, p = 0.023) and 12 sessions (Z = -2.517, p = 0.012). MPO levels were significantly reduced in the massage group post-intervention (F [1, 22] = 7.956, p = 0.01; t [11] = 2.959, p = 0.013), indicating anti-inflammatory effects. A significant time effect was also observed for beta-endorphin (F [1, 22] = 6.632, p = 0.017), with reduced levels after massage (t [11] = 3.321, p = 0.007). No significant changes were found in anxiety, blood pressure, heart rate, BDNF, cortisol, SOD1, or eNOS. Conclusions:Automated massage chair therapy significantly alleviated depression, stress, and musculoskeletal pain, particularly in the calves and lower back, with modest biochemical changes such as reduced MPO and beta-endorphin levels. These findings support massage chair use as a convenient, noncontact strategy to enhance psychological and physical well-being in healthcare professionals.

Rheumatoid arthritis (RA) pain is a debilitating symptom often persisting despite reduced inflammation, possibly due to dysregulated pain pathways. The study aimed to determine the effects of CORM-2 and Ifenprodil on nociceptive mechanisms involving NMDAR-2B and BDNF in thalamus of chronic polyarthritis rat mimicking RA. Eighty rats were randomly assigned into five groups: non-arthritic(N), arthritic control(A), arthritic groups treated with either CORM-2 (A+CORM-2), Ifenprodil (A+Ifenprodil), or Diclofenac (A+Diclofenac). Chronic polyarthritis was induced by injecting complete Freund’s adjuvant (10mg/mL) in right footpad of the rats and intrathecal treatments were given for 7 days (Day-15 to Day-22). Pain behaviour tests evaluating tactile allodynia and thermal hyperalgesia development were conducted on Day-0 (baseline), Day-14 (pre-treatment), and Day-23 (post-treatment). Thalamus was collected for further molecular analyses. There was significant development of tactile allodynia and thermal hyperalgesia detected in arthritic rats (p<0.05) which were significantly reversed by CORM-2 and Ifenprodil treatments (p<0.05). Significant upregulation of mRNA level with increased BDNF and NMDAR-2B protein expression was detected in bilateral thalamic VPL regions (p<0.05). These proteins expression and mRNA levels were significantly reduced and downregulated with the treatments of CORM-2 and Ifenprodil (p<0.05).CORM-2 and Ifenprodil exert anti-nociceptive effects possibly by modulating thalamic nociceptive mechanisms through NMDAR-2B/BDNF signalling inhibition in chronic polyarthritis rat. This study provides insights into understanding possible mechanisms leading to RA pain for future therapeutic development and chronic pain management.

Diabetes mellitus (DM) and its complications continue to impose a substantial burden on healthcare systems worldwide. Diabetic neuropathy (DN) is one of the most common chronic microvascular and neurodegenerative complications of DM. It is clinically characterized by allodynia, hyperalgesia, and abnormal or absent nerve fiber sensation, which collectively contribute to poor quality of life, sleep disturbances, depression, and increased mortality. Although several pharmacological agents are available to alleviate DN-related symptoms, their limited long-term efficacy and adverse side effects underscore the urgent need for novel therapeutic approaches. This limitation may be attributed to an incomplete understanding of the underlying mechanisms of DN. Accumulating evidence has highlighted the contribution of glial cells including astrocytes, microglia, and oligodendrocytes to the pathogenesis of DN. However, the specific role of astrocytes remains insufficiently defined. Therefore, this review provides a comprehensive evaluation of current knowledge regarding astrocyte involvement in DN mechanisms, with the goal of clarifying their contribution to disease progression and identifying potential therapeutic targets.

IntroductionThe neuroinflammatory response was seen to impact the formation of phosphorylated tau protein in Alzheimer's disease (AD). This study aims to investigate the molecular mechanism of minocycline in reducing phosphorylated tau protein formation in the hippocampus of lipopolysaccharide (LPS)-induced rats.MethodsFifty adult male Sprague Dawley (SD) rats were randomly allocated to 1 of 5 groups: control, LPS (5 mg/kg), LPS + minocycline (25 mg/kg), LPS + minocycline (50 mg/kg) and LPS + memantine (10 mg/kg). Minocycline and memantine were administered intraperitoneally (i.p) for two weeks, and LPS was injected i.p. once on day 5. ELISA was used to determine the level of phosphorylated tau protein in SD rats' hippocampal tissue. The density and expression of Toll-like receptor-4 (TLR-4), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-k beta), tumour necrosis factor-alpha (TNF-alpha), and cyclooxygenase (COX)-2 were determined using Western blot and immunohistochemistry.ResultsMinocycline, like memantine, prevented LPS-induced increasein phosphorylated tau protein level suggested via reduced density and expression of TLR-4, NF-k beta, TNF-alpha and COX-2 proteins in rat hippocampal tissue. Interestingly, higher doses were shown to be more neuroprotective than lower doses.ConclusionThis study suggests that minocycline suppresses the neuroinflammation signalling pathway and decreased phosphorylated tau protein formation induced by LPS in a dose-dependent manner. Minocycline can be used as a preventative and therapeutic drug for neuroinflammatory diseases such as AD.

Background: Tuberous sclerosis complex (TSC) is a rare autosomal dominant multisystem disease resulting from hyperactivation of the mammalian target of rapamycin (mTOR) signaling pathway. This study aimed to measure the quantitative impact of publications in TSC. Materials and methods: We analysed TSC literature obtained from the Scopus database using Bibliometrix R Package and VOSviewer software. Annual publication trends, most productive and collaborative authors/institutions/ countries, most cited articles, most popular journals and author’s keywords were presented using standard bibliometric indicators. Results and discussion: A total of 5375 documents on TSC were published from 1960 to December 2020, with an increasing trend. The three primary contributing writers were Curatolo P, Kwiatkowski DJ, and Thiele EA, with the United States and its institutions being the largest contributor. The research identified two of the most referenced papers as TSC’s seminal pieces. The top journals that published TSC research were medical journals, namely Journal of Child Neurology, Epilepsia, and Pediatric Neurology. mTOR inhibitor, everolimus, sirolimus, mTORC1, mTOR pathway, autophagy, inflammation, infant, intellectual disability, white matter, TSC-associated neuropsychiatric disorders, TOSCA and quality of life were relatively newer author’s keywords and may indicate the future research hotspots in TSC research. Conclusion: Over the last few decades, TSC research has grown in importance, particularly in the field of clinical medicine. Therapeutic components targeting TSC-related pathways, the utilisation of TSC as disease models and long-term safety studies will be future research areas. Bangladesh Journal of Medical Science Vol. 23 No. 01 January’24 Page : 18-28

Purpose/Aim Neuroinflammation and oxidative stress have been encountered in neurodegenerative diseases such as Alzheimer's disease (AD). However, the neuroprotective effects of minocycline against lipopolysaccharide (LPS)-induced glial cells activation and oxidative stress damage in the medial prefrontal cortex (mPFC) of rats are still elusive. The purpose of this study is to investigate the effects of minocycline and memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, on the microglia and astrocytes expression, as well as oxidative stress levels in the mPFC of LPS injected rats. Materials and Methods Fifty adult Male Sprague Dawley rats were divided into five groups: control, LPS (5 mg/kg), LPS treated with minocycline (25 mg/kg), LPS treated with minocycline (50 mg/kg) and LPS treated with memantine (10 mg/kg). The immunohistochemistry and western blotting were used to analyse the expressions and densities of microglia marker (Iba-1) and astrocyte marker, (GFAP) while enzyme-linked immunosorbent assay (ELISA) was used to measure the protein carbonyl (PCO), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) levels. Results In comparison to the control group, the expression and density of Iba-1 and GFAP were significantly enhanced in the LPS group (p < 0.05). LPS group also exhibited significantly higher levels of PCO and MDA (p < 0.05) and significantly lower levels of CAT and SOD (p < 0.05) when compared to the control group. Both minocycline and memantine-treated LPS rats were able to protect against these effects. Conclusion Minocycline, like memantine treatment, reduces oxidative stress in the mPFC of LPS rats via inhibition of glial cells activation.

Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by the development of benign hamartomas in various organs, including renal angiomyolipoma. The current medical standard treatment for TSC-associated renal angiomyolipoma involves the use of a mammalian target of rapamycin (mTOR) inhibitor. To better understand the molecular basis of this treatment approach, our study aimed to identify differentially expressed genes (DEGs) in the UMB1949 cell line following treatment with asiaticoside and asiatic acid and compared them to the effects of everolimus treatment. Using the RT2 Profiler polymerase chain reaction (PCR) array panel, we systematically analyzed the expression patterns of these DEGs, utilizing gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGGs) pathway analyses to elucidate the underlying mTOR inhibitory mechanisms in UMB1949. Our results revealed that all three substances shared five DEGs (four upregulated: CAB39, PRKCE, RRAGC, RPS6KA5, and one downregulated: DEPTOR), as well as seven common GO terms and KEGG pathways, suggesting that the inhibitory activity against mTOR closely mirrors that of everolimus. Moreover, we identified a significant overlap in DEGs involved in cell inhibition via the mTOR pathway across all treated groups. Based on the comprehensive analysis of DEG bioinformatics data, we hypothesized that asiaticoside and asiatic acid exhibit functions comparable to everolimus, with asiaticoside displaying a closer similarity to everolimus than asiatic acid. These findings provide valuable insights into the molecular mechanisms and potential mTOR inhibitors for TSC-associated renal angiomyolipoma and establish a crucial link between our study and the current therapeutic landscape of TSC.

Background and aim Centella asiatica (L.) Urb. (Apiaceae) is a renowned medicinal plant being used in the Ayurvedic system for its pharmacological effects on the central nervous system such as rejuvenating, sedative, anxiolytic and memory-enhancing properties. The present study was designed to investigate the effect of Centella asiatica (CA) extract on inflammatory responses induced by lipopolysaccharide (LPS) and resulting changes in cognitive behavior. Materials and methods Adult male Sprague-Dawley rats were divided into 4 groups as control, LPS, CA and LPS + CA. The treatments with LPS (5 mg/kg) were intraperitoneally (i.p) injected on day 4 and CA ethanol extract (200 mg/kg) were given orally for 14 days. Morris Water Maze (MWM) test was performed to assess spatial learning and memory performance. Acute oral toxicity of the extract at the highest dose of 5000 mg/kg was also conducted. Results Single administration of LPS was able to significantly elicit learning and memory impairment (p < .05) when compared to the control groups. Treatment with CA significantly improved the impaired learning ability in which the LPS + CA rats took the shortest time and route to find the hidden platform (15.85 +/- 2.68 s (p < .001); 352.43 +/- 88.10 cm (p < .001) on day 5) and induced differential cytokine responses in the blood. No mortality and no significant variation in the body and organ weights between the control and the treated group was observed after 14 days of acute toxicity study. Hematological analysis and biochemical parameters revealed no toxic effects of the extract. Pathologically, neither gross abnormalities nor histopathological changes were observed. Discussion and conclusion Centella asiatica extract exhibited significant learning and memory enhancement potential in animal model. Hence, indicating its putative preventive therapeutic effects in neuroinflammation related diseases. KEY MESSAGE A single dose of lipopolysaccharide (LPS) (5 mg/kg) administered systemically to mimic the consequences of LPS-induced inflammatory responses was able to affect some behavioral modification of spatial memory at the time point of study. The study showed that the learning capability during the training trial was restored or ameliorated with the pre-emptive treatment of Centella asiatica extract (200 mg/kg). Centella asiatica extract improves spatial memory, learning deficits and regulates proinflammatory responses in systemic LPS-treated rats.

There is growing evidence that diabetes can induce cognitive decline and dementia. It is a slow, progressive cognitive decline that can occur in any age group, but is seen more frequently in older individuals. Symptoms related to cognitive decline are worsened by chronic metabolic syndrome. Animal models are frequently utilized to elucidate the mechanisms of cognitive decline in diabetes and to assess potential drugs for therapy and prevention. This review addresses the common factors and pathophysiology involved in diabetes-related cognitive decline and outlines the various animal models used to study this condition.