Objective: Hypercalcemia allied with thiazide diuretics is a widely acknowledged clinical presentation. Hence, the purpose of this investigation was to ascertain the prevalence of hypercalcemia and hypercalcemia linked to thiazides and to evaluate serum phosphorous, 25- hydroxyvitamin D, and parathyroid hormone (PTH). Methods: This prospective, cross-sectional research study involved all patients, including outpatients, and was conducted over a 12-month period. Between December 2017 and December 2018, an aggregate of 373 patients were enrolled. All patients with hypercalcemia (albumincorrected serum calcium > 10.8 mg/dL) had their medical information put on a proforma, together with the results of any tests (such as parathyroid hormone (PTH), 25-hydroxyvitamin D, and serum phosphorus). Results: Out of 373 subjects, 7 (2%) were hypercalcemic. The mean corrected calcium levels in the normo-calcemic group were 9.46 ± 0.60 mg/dL (95% CI, 9.4 – 9.5), and that in the hypercalcemic group were 11.68 ± 0.82 mg/dL (95% CI, 10.9 – 12.4). Of the seven cases of hypercalcemia, 2 patients (28.6%) had thiazide-associated hypercalcemia (TAH) along with primary hyperparathyroidism (PHPT). Of the remaining 5 hypercalcemia patients, two more had PHPT, and one (14.3%) had hypervitaminosis D, whereas no cause was mentioned in the remaining 2 patients. Among the 4 PHPT patients, corrected calcium was slightly higher in those with TAH vs those without TAH, though the difference was statistically insignificant (11.32 ± 0.43 vs 11.14 ± 0.39 mg/dL; P > 0.7). Conclusion: TAH is the second primary cause of asymptomatic hypercalcemia after PHPT. Thus, close coordination between the clinicians, pharmacology, pharmacovigilance, and the biochemistry department may help in identifying these cases.

INTRODUCTION:Among premenopausal women, polycystic ovarian syndrome (PCOS) is one of the most ubiquitous endocrine and metabolic conditions. Abdominal adiposity, insulin resistance, obesity, metabolic diseases, and cardiovascular hazards are often associated with PCOS. This investigation aims to decipher the influence of oral Vitamin D3 supplementation (2000 IU/day for three months) on glucose metabolism in PCOS women. METHODS:123 subjects (females 16 to 40 years of age) were arbitrarily allocated to three cohorts (n = 41 in each cohort) Each participant received two tablets daily and a sachet every month for three months (Group I: Vitamin D3 Tablets + placebo sachets; Group II: Placebo Tablets + Vitamin D3 sachets; Group III: Tablets + Placebo sachets). RESULTS:Among 123 PCOS subjects, 93.4% exhibited hypovitaminosis D. The baseline 25-hydroxyvitamin D (25(OH)D) concentration of 13.76 (SD ± 10.61) ng/ml increased by 86.84% post-intervention. Groups I and II (active group) depicted substantial diminution in pre-treatment fasting and 2-h blood glucose, with no substantial change in the HOMA-IR. Group III (placebo) showed no improvement in vitamin D status or HOMA-IR. Overall, we observed no substantial HOMA-IR improvement with vitamin D subjunction. However, subgroup analysis revealed a statistically significant enhancement in HOMA-IR for subjects achieving a two-fold upsurge in post-supplementation 25(OH)D levels (≥ 20 ng/ml) compared to those without this increase (p = 0.025). DISCUSSION:The cohort's mean blood 25-hydroxyvitamin D concentrations were successfully boosted by 84% by Vitamin D3 dosage; yet, the influence on insulin resistance markers displayed a subtle complexity. A relationship was found amid the absolute variation in HOMAIR and the percentage variation in Vitamin D. Nevertheless, there was no substantial general alteration in the mean HOMA-IR across different subgroups. CONCLUSION:Vitamin D3 supplementation improves glucose metabolism, as demonstrated by lower fasting and 2-hour blood glucose levels, but overall has no substantial repercussion on measures of insulin sensitivity like HOMA-IR. A larger vitamin D3 dose and an extended follow-up study are essential to comprehend the complex physiology of vitamin D and glucose homeostasis.

Alzheimer’s disease (AD) is a chronic, multifactorial neurodegenerative disorder characterized by progressive cognitive decline and memory loss. Pathological hallmarks include extracellular amyloid-β (Aβ) deposition and intracellular neurofibrillary tangles (NFTs) in brain cells, which drive neuronal degeneration and dementia. Current drugs provide only symptomatic relief, with limited efficacy and adverse side effects, underscoring the need for novel therapeutics. In this study, phytochemicals from Curcuma longa were screened for drug-likeness using ADME and pharmacokinetic analyses, identifying curcuminoids—curcumin, demethoxycurcumin, and bisdemethoxycurcumin—as bioavailable candidates. Molecular docking (MD) revealed strong binding affinities for AD therapeutic targets, including acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), glycogen synthase kinase-3β (GSK-3β), β-secretase, and γ-secretase (− 11.07 to − 22.70 kcal/mol), suggesting multi-target inhibitory potential. MD simulations (100 ns) demonstrated structural stability, with demethoxycurcumin showing the lowest RMSD values (~ 0.13–0.18 nm for AChE). MM-GBSA free energy calculations confirmed favorable binding (ΔG_binding − 23.35 kcal/mol for β-secretase–demethoxycurcumin and − 21.68 kcal/mol for BuChE–demethoxycurcumin). In vivo validation using an Aβ42-expressing Drosophila model showed dose-dependent reductions in cholinesterase activity (60–75% at 5 mg/mL, p < 0.05), suppression of AD-associated proteins (Aβ42: ~50–60%; BACE1: ~30–40%; GSK-3β: ~50–60%; KEAP1: ~30–40%), lifespan extension (27.98 → 38.66 days, p < 0.001), and improved motor activity (climbing index ~ 0.70 → ~0.90–1.00, p < 0.001). Collectively, these findings highlight curcuminoids as a promising multi-target-directed ligand for AD therapy, warranting further validation in higher-order animal models.

Background: Hepatotoxicity is a major complication of antitubercular therapy (ATT). Herbal remedies might alleviate ATT-induced hepatotoxicity owing to a wide range of bioactive phytoconstituents. Objectives: The present study evaluated the hepatoprotective effects of Callicarpa lanata (L.) leaves against ATT. Methods: The ethanolic extract of C. lanata (L.) leaves (EECL) was prepared, and rutin was analyzed in the extract using HPTLC. ATT (Isoniazid, Rifampicin, Pyrazinamide, Ethambutol) was administered in Wistar rats to induce hepatotoxicity, and EECL (200 and 400 mg/kg) or silymarin (100 mg/kg) was given orally for 35 days. Results: EECL ameliorated (p < 0.05) different blood biomarkers (aminotransferases, alkaline phosphatase, serum protein, γ-glutamyl transpeptidase, lactate dehydrogenase, and total bilirubin) of liver injury against ATT. EECL enhanced (p < 0.05) hepatic sulfhydryl (-SH) group antioxidants along with a substantial upsurge in antioxidant enzymes and Nrf-2 levels and decreased hepatic lipid peroxidation. A decrease (p < 0.05) in ATT-induced hepatic pro-inflammatory cytokines, NF-κB, and liver lysosomal (cathepsin D and β-galactosidase) and cytochrome P450 enzymes (CYP2E1 and CYP3A4) was observed in EECL-treated rats. Histopathological studies showed improved hepatocellular structure against oxidative- and inflammation-induced necrosis and other tissue modifications by EECL. The HPTLC analysis showed the presence of rutin in the crude extract. Conclusion: Evidence suggests that C. lanata protects against ATT-induced hepatic injury, and rutin might be responsible for the beneficial effects. C. lanata leaves have therapeutic potential in mitigating drug-induced (ATT) hepatotoxic effects.

Transcription factor PPAR-γ is predominantly found in adipose tissue, liver, and brain. PPARs form heterodimers, interact with ligands, and regulate the expression of the genes of the PPAR-γ downstream regulatory pathways. PPAR-γ is critical in regulating many physiological processes, including adipogenesis, glucose metabolism, fatty acid metabolism, energy homeostasis, and inflammation. This review is on the functions of PPAR-γ and how dysregulation of activity or expression of PPAR-γ can lead to obesity and Alzheimer's disease (AD). The PPAR- γ agonist inhibited the downregulated pathways, such as Wnt/β-Catenin and JAK-STAT pathways, both involved in activating NF-kB. PPAR-γ has a significant role in the APOE (Apolipoprotein E) gene expression, which reduces reducing obesity, inhibits amyloid aggregation, prevents hyperphosphorylation of tau, and inhibits dysregulation of autophagy. This review provides a perspective on the intricate interplay between PPAR-γ, obesity, and AD, focusing on the molecular mechanisms and potential therapeutic implications.

Long-term hyperglycemia and insulin dysfunction deteriorate peripheral nerve functions, leading to sensory loss, spontaneous pain, and hypersensitivity (i.e., allodynia and hyperalgesia). Evidence indicates glucose-induced upregulation of the Wnt/β-catenin mechanism in diabetic peripheral neuropathy (DPN). Eriodictyol (Ed) has shown protective effects against glucotoxicity. The present study explored the bioactivity of Ed in streptozotocin (STZ) induced DPN and the role of the Wnt/β-catenin pathway. Ed or gabapentin (Gpn), or methyl vanillate (MV) was administered in Wistar rats for 4 weeks, starting 6 weeks after STZ administration. Ed ameliorated the mean body weight and mitigated polydipsia and polyphagia in DPN rats. The data indicated that Ed attenuated hyperglycemia, glycosylated hemoglobin (HbA1c) levels, and HOMA-IR, and enhanced circulating insulin levels and HOMA-β against STZ-induced DPN. MV (Wnt/β-catenin activator) caused a significant increase in STZ-induced hyperglycemia, HbA1c, HOMA-IR, and further decreased the insulin levels and HOMA-β in STZ-treated rats. Ed attenuated oxidative stress, inflammatory expression, level of advanced glycation end products, and nuclear factor kappa B in the sciatic nerve of STZ-treated neuropathic rats, and MV further potentiated these markers triggered by STZ. Interestingly, Ed and Gpn attenuated mRNA expression of Wnt1/β-catenin in the sciatic nerve of neuropathic rats. Hyperalgesia and allodynia were significantly ameliorated in Ed or Gpn-treated rats against DPN. Furthermore, Ed ameliorated the biochemical biomarkers, histopathological characteristics, and nociceptive-like responses in STZ and MV-treated rats. It is concluded that Ed can alleviate the pathogenic course of DPN. Wnt/β-catenin pathway might be involved in the eriodyctiol-triggered mitigation of nociceptive-like responses in diabetic rats.

The existing study aims to explore the different aspects of paracetamol (PCM) and high-fat high fructose diet (HFHF) produced non-diabetic and diabetic liver damage with references to multiple biochemical markers in the context of pharmacological therapies with respect to their adipogenic inhibition and hepatoprotective outcomes. Pterostilbene, Arbutin, and Purpurin were used for managing the HFHF and PCM-induced liver-related complications in rodents 28-week and 8-day models, respectively. The biochemical, oxidative stress parameters were measured for the assessment of elected interventions. For the sake of scientific credibility, the expression of fatty acid synthase, which is individualistically linked to diabetes-related fatty liver diseases, was assessed using real-time polymerase chain reaction. HFHF diet ingestion for 28 weeks noticeably (p < 0.05) caused a significant expansion of glucose levels in comparison to normal diet-treated investigational rodents, while the reverse was observed in intervention-treated sets in comparison to the HFHF-treated groups. The situation was upturned in the case of PCM-treated rodents as there was insignificant augmentation in the point of glucose which clearly depicted the distinction between non-diabetic and diabetic liver injury models. It is hypothesized that dropping free fatty acid levels through FAS inhibition will recover insulin resistance and assuage non-diabetic and diabetic liver injury models.

Background: Mimusops elengi (Linn.) has high medicinal value and is a native plant of India. In the traditional system of medicine, the bark of M. elengi was used as cardiotonic, alexipharmic, stomachic, anthelmintic, tonic, and tooth-protectant that might be associated with antioxidant and antimicrobial effects. Microorganisms are an integral part of our buccal cavity and intestines, however, a change in normal microflora can result in pathological manifestations. Objective: The current study attempts to evaluate the antioxidant activity of M. elengi (Linn.) stem bark extracts using in-vitro methods and the efficacy of M. elengi (Linn.) stem bark extracts against Gram-negative bacteria and fungal strains. Methods: Extracts (aqueous and ethanolic) were prepared using a Soxhlet assembly and rotavapor. The extracts were subjected to phytochemical screening and in-vitro antioxidant and antimicrobial tests. Results: The ethanolic and aqueous extracts of M. elengi stem bark showed appreciable DPPH free radical scavenging, reducing power, and nitric oxide inhibitory activities with a concentration-dependent increase in their effects. The ethanolic extract showed better antioxidant activity relative to the aqueous extract. Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, and Salmonella typhi growth were suppressed by the M. elengi extracts. Both extracts showed maximum activity against S. typhi, while the ethanolic extract had better antibacterial and antifungal (S. cerevisiae, P. chrysogenum, and A. fumigatus) activity relative to the aqueous extract. Conclusions: The findings of the present study conclude that aqueous and ethanolic extracts of M. elengi (L.) stem bark showed potent antioxidant and antimicrobial activity.

Hypoxia-induced brain damage can cause consciousness, memory failure and death. HK2 and TPI1 were investigated to see how they change hypoxia sensitivity in neurons and non-neurons. Hypoxia sensitivity is determined by the differential overexpression of both important glycolytic enzymes in neuronal and non-neuronal cells. C6 glioma cells expressed greater HK2 and TPI1 protein than neuro 2A cells, which were more sensitive to hypoxia-induced cell death by MTT and lactate dehydrogenase leakage assay. After 48 h of hypoxia, C6 glioma cells displayed substantial protein upregulation of HK2 and TPI1 glycolytic proteins but not mRNA. Hypoxia did not raise HK2 and TPI1 mRNA transcription, pointing at post-transcriptional protein regulation. Using di-cistronic and promoter-less di-cistronic assays, we discovered significant IRES regions in HK2 and TPI1 mRNA’s 5′UTR, more active in C6 glioma cells with polypyrimidine tract binding (PTB) protein. We concluded that non-neuronal cells varied in HK2 and TPI1 overexpression, altering their vulnerability to hypoxia-induced cell death. Adjusting HK2, TP1 and PTB levels may prevent hypoxia-induced brain cell death. These results offer new information on glycolytic enzyme modulation under hypoxia, crucial for comprehending cell survival in hypoxic situations. This could affect situations like neurodegenerative illnesses or ischaemic injuries, where hypoxia-induced cell death is crucial.

Abstract: Depression has a high prevalence and associated comorbidities. It is still unknown what the molecular basis of depression is, regardless of many theories that have been put up to explain it. Many researchers investigate that present-day therapies for depression are ineffective due to their low efficacy, delayed onset of action (typically two weeks), and adverse effects. Novel medications that operate more quickly and effectively are thus needed. Several novel molecules (e.g., ketamine, buprenorphine) have been proven to produce quick and dependable antidepressant benefits in depressive patients who are resistant to treatment; yet, questions about their effectiveness, possible abuse, and adverse effects persist. The molecular basis and pharmacological interventions for depression were included in this study. Even if pharmaceutical treatments for depression have mostly failed to alleviate the condition, identifying and addressing possible risk factors in an effort to reduce the prevalence of this psychiatric disease is beneficial for public health. We emphasized the neuroanatomy and etiopathogenesis of depression, along with a discussion of the putative pharmacological mechanisms, novel targets, research hurdles, and prospective therapeutic futures.

BACKGROUND:Cancer is amongst the most dreadful ailments of modern times, and its impact continuously worsens global health systems. Early diagnosis and suitable therapeutic agents are the prime keys to managing this disease. Metabolomics deals with the complete profiling of cells and physiological phenomena in their organelles, thus helping in keen knowledge of the pathological status of the disease. It has been proven to be one of the best strategies in the early screening of cancer. OBJECTIVE:This review has covered the recent updates on the promising role of metabolomics in the identification of significant biochemical markers in cancer-prone individuals that could lead to the identification of cancer in the early stages. METHODS:The literature was collected through various databases, like Scopus, PubMed, and Google Scholar, with stress laid on the last ten years' publications. CONCLUSION:It was assessed in this review that early recognition of cancerous growth could be achieved via complete metabolic profiling in association with transcriptomics and proteomics. The outcomes are rooted in various clinical studies that anticipated various biomarkers like tryptophan, phenylalanine, lactates, and different metabolic pathways associated with the Warburg effect. This metabolite imaging has been a fundamental step for the target acquisition, evaluation of predictive cancer biomarkers for early detection, and outlooks into cancer therapy along with critical evaluation. Significant efforts should be made to make this technique most reliable and easy.

Elevated reactive species and AGEs contribute to deregulation of transcription factors e.g., NF-κB and Nrf2 in diabetic peripheral neuropathy (DPN). Okanin, a bioactive chalcone, is active against redox imbalance, immune response, and pro-inflammatory events. The current investigation assessed effects of okanin in streptozotocin-induced DPN in rats. Wistar rats were divided into 6 groups (n = 6): Control, DPN, Okanin 2.5, Okanin 5, Okanin 10, and Gpn (Gabapentin). After 6 weeks of streptozotocin (55 mg/kg) injection, okanin (2.5, 5, 10 mg/kg), and gabapentin (50 mg/kg), were administered for 4 weeks. The streptozotocin-induced reduction in body weight, and increased feed/water intake, insulin, glucose, and HbA1c levels were mitigated by okanin or gabapentin. In DPN rats, Okanin or gabapentin ameliorated insulin resistance and β-cell function, inflammatory indices, and oxidative stress in the sciatic nerve of rodents thereby culminating in a decrease in hyperalgesia and allodynia. Okanin and streptozotocin-treated rats had significantly declined levels of AGEs, the receptor for AGEs, and NF-κB, and an upsurge in Nrf2 expression. In streptozotocin-induced DPN model, okanin ameliorates nociceptive-like responses by regulating the AGEs/NF-κB/Nrf2 pathway, suggesting that okanin has therapeutic value against DPN which needs further studies involving human subjects.

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Point of Care Diagnostics (POCD) is quintessential in hospitals and the healthcare sector as the secants uplift the quality of medical care and the life of a patient by facilitating quick identification of the underlying pathological condition. Nanotechnology can provide opportunities and has potential in the development of new-age sensing/diagnostic tools. Owing to extraordinary features (e.g., higher density, effective catalysis, good conduction, biocompatibility, inertness, and greater surface-to-volume ratio), gold nanoparticles (AuNPs) are frequently employed in POCT (Point-of-Care-Testing). Gold nanoparticles-based colorimetric methods are widely used in the rapid, sensitive, and selective detection of analytes/target molecules. AuNPs description is critical for their possible utility in prophylaxis, diagnostics, and treatment of an ailment. AuNPs interact with organic/inorganic target molecules to generate colorimetric shift that enables the accurate, precise, and subtle recognition of biologicals (e.g., microorganisms, cellular components, and proteins) and metal ions. This review focused on the need for AuNPs-based colorimetric application in prophylaxis, diagnostics, and treatment in healthcare and reviewed the future outlook of these AuNPs for biological applications. Different synthesis methods of AuNPs, their morphology, and characterization, including their surface functionalization, will be discussed in detail. AuNPs are very much preferable nanomaterials owing to exclusive optical, electrical, and photothermal features. AuNPsbased colorimetric biosensors are simple and possess great utility, yet these offer a robust technique to enable visual, quantitative analysis.

Liver regeneration is a crucial process involved in cellular proliferation, differentiation, and tissue repair. Calcium signaling impact key pathways like hepatocyte growth factor-Met-tyrosine kinase (HGF-Met) transduction pathway, the epidermal growth factor receptor (EGFR) signaling and Ca-mediated nuclear SKHep1 cell proliferation pathway. Intracellular hepatocyte calcium stores are considered as base for the induction of ca-mediated regeneration process. Calcium signaling interplays with HGF, TGF-β, and NF-κB signaling, influence stem cell behavior and triggers MAPK cascade. The mitochondria calcium is impacting on liver rejuvenation by regulating apoptosis and cell division. In conclusion, it is stated that calcium-signaling holds promise for therapeutic liver interventions.

Chronic fatigue syndrome (CFS) is a complex condition marked by severe exhaustion that lasts at least 6 months. The global prevalence of CFS ranging between 0.4% and 2.5% is growing. Women are affected by CFS more often than men. It is considered a common condition in developed countries. There is no approved treatment for CFS but symptoms can be managed and controlled persistent exhaustion causes significant impairment in daily routine activities. Lowered ATP synthesis, mitochondrial impairment, decreased oxidative phosphorylation, disruption of the hypothalamic–pituitary–adrenal (HPA) axis, and an imbalance of brain neurotransmitters play a major role in the pathophysiology of CFS. The purpose of the present study is to figure out the several plants that are used as a source of medication in chronic fatigue syndrome (CFS) and its current therapeutic approach. The Indian medicinal herbs described in this article are very efficacious in the management of chronic fatigue syndrome symptoms due to the presence of phytochemicals. This review article also covers the current therapeutic approach for chronic fatigue syndrome in a concise form that comprises CBT (Cognitive based therapy), GET (Graded exercise therapy), usage of immunoglobins, psychodynamic counseling, and yoga therapy that includes isometric yoga and yoga nidra are very beneficial in alleviating the symptoms of chronic fatigue syndrome. Antidepressants, immunomodulatory agents, and corticosteroids come under conventional medication for CFS. This article explores different Indian medicinal herbs, their pharmacological properties, and their potential role and current treatments for reducing the severity of symptoms of chronic fatigue syndrome.

Evidence indicates that anxiety disorders arise from an imbalance in the functioning of brain circuits that govern the modulation of emotional responses to possibly threatening stimuli. The circuits under consideration in this context include the amygdala’s bottom-up activity, which signifies the existence of stimuli that may be seen as dangerous. Moreover, these circuits encompass top-down regulatory processes that originate in the prefrontal cortex, facilitating the communication of the emotional significance associated with the inputs. Diverse databases (e.g., Pubmed, ScienceDirect, Web of Science, Google Scholar) were searched for literature using a combination of different terms e.g., “anxiety”, “stress”, “neuroanatomy”, and “neural circuits”, etc. A decrease in GABAergic activity is present in both anxiety disorders and severe depression. Research on cerebral functional imaging in depressive individuals has shown reduced levels of GABA within the cortical regions. Additionally, animal studies demonstrated that a reduction in the expression of GABAA/B receptors results in a behavioral pattern resembling anxiety. The amygdala consists of inhibitory networks composed of GABAergic interneurons, responsible for modulating anxiety responses in both normal and pathological conditions. The GABAA receptor has allosteric sites (e.g., α/γ, γ/β, and α/β) which enable regulation of neuronal inhibition in the amygdala. These sites serve as molecular targets for anxiolytic medications such as benzodiazepine and barbiturates. Alterations in the levels of naturally occurring regulators of these allosteric sites, along with alterations to the composition of the GABAA receptor subunits, could potentially act as mechanisms via which the extent of neuronal inhibition is diminished in pathological anxiety disorders.