Biomedicine (Journal)
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Neuroprotection of paeoniflorin as antidepressant candidate
Background: Depression is one of the common mental disorders worldwide, and currently used antidepressants have undesirable effects; therefore, the development of new antidepressants without side effects is urgently needed. Paeoniflorin (PF) exhibits various pharmacological activities, including anti-inflammatory, antioxidant, and neuroprotective effects. NMDA receptors in the hippocampus play a vital role in the pathophysiology of depression. Due to the scarcity of reports on the neuroprotection of PF on NMDA-induced excitotoxicity in the hippocampus, the present study aims to investigate the effects of PF on NMDA-mediated EPSP and calcium influx in the hippocampus to evaluate the potential of PF as an antidepressant.
Methods: In order to investigate the effects of PF on the NMDA receptor in the hippocampus, the hippocampal slices, primary-cultured hippocampal neurons, and in silico molecular docking analysis of PF with the NMDA receptor were used.
Results: PF (2 mM) significantly depressed the NMDA-mediated EPSPs, resulting in a 50% inhibition. The intracellular calcium level in primary-cultured hippocampal neurons was 102.67 nM, and 520.36 nM after NMDA (125 mM) treatment. With NMDA and PF co-treatment, the calcium level was 204.58 mM, showing a 60.68% decrease. After NMDA was co-treated with 1 μM ruthenium red (RuR), the calcium level increased (from 534.58 nM to 665.68 nM). Additionally, co-treatment with PF significantly decreased the calcium level (468.05 nM, representing a 29.50% decrease). In the presence of NMDA and 1 mM w-conotoxin MVIIC (w-Cono) co-treatment, the calcium level was 496.29 nM. In the presence of NMDA, w-Cono, and RuR, the calcium level was 568.5 nM. Additionally, NMDA, w-Cono, RuR, and PF co-treatment significantly decreased the calcium level to 270.94 nM. In silico molecular docking analysis revealed a binding energy of -48.5188 Kcal/mol for PF with the NMDA receptor.
Conclusions: PF binds to the NMDA receptor, exhibits neuroprotection, and contributes to its potential as an antidepressant
Prophylactic Effect of Omega-3 Polyunsaturated Fatty Acids Monotherapy in Preventing Recurrent Major Depressive Disorder: A Randomized Controlled Trial
Background: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have demonstrated efficacy as adjunctive treatment for MDD. In fact, fewer studies assessed the prophylactic properties of n-3 PUFAs as monotherapy on the recurrence of MDD.
Aims: This study aimed to assess the prophylactic effect of n-3 PUFAs monotherapy against recurrent MDD.
Methods: We conducted a 6-month randomized controlled trial to assess the prophylactic effect of n-3 in preventing recurrent MDD. We assigned 60 remitted MDD patients to the n-3 group (n = 30) and placebo (n = 30). Furthermore, we assessed the difference in depression severity and MDD recurrence based on the 21-item Hamilton Rating Scale for Depression (HRSD) at months 1, 2, 3, 4, and 6 between groups. The recurrent event of MDD was defined as an HRSD score \u3e20. Furthermore, biochemical parameters in plasma were assessed as the secondary outcomes.
Results: There was no significant difference in the HRSD score between the n-3 group and placebo each month (p-value \u3e 0.05). However, our findings have implicated that omega-3 monotherapy for MDD contributed to a lower recurrence rate compared to the placebo group at month 6 (p-value = 0.035). Omega-3 supplementation was superior to placebo to preventing recurrent MDD analyzed using Kaplan-Meier survival analysis over a 6-month study period (p-value = 0.041). In comparison, the eicosapentaenoic acid (EPA) plasma level of the n-3 group at the end point of study was significantly higher than the placebo (p-value = 0.023), but not for docosahexaenoic acid (DHA) (p-value = 0.119).
Conclusion: Our study concluded that n-3 PUFAs monotherapy demonstrated a prophylactic effect on the recurrence of MDD
Russell’s viper envenomation: The Challenge of Diagnosis
Russell’s viper envenomation is rare in Taiwan, and its typical clinical presentations, including consumption coagulopathy, acute renal failure, haemolysis, and increased capillary permeability, have been reported in the literature as case reports or series. Here, we report a case with an atypical presentation, and suspected to be a Russell’s viper bite due to the distinct characteristics of the snake and some progressive clinical signs/symptoms. He returned to health successfully after the correct antivenom was administered, and envenomation was ultimately confirmed by venom detection in the patient’s serum and urine samples
Unveiling Role of Oncogenic Signalling Pathways in Complicating Breast Cancer
Heterogeneous nature of breast cancer has significantly affected the overall survival, disease free survival and progression free survival amongst the diseased individuals. Metastasis of cancerous cells to distant sites including bone, lungs, liver, lymph node and others have further exhilarated the adverse effects. However, ER, PR and HER-2 are responsible for normal physiological development of women but in altered conditions they may act as initiator or progressor and so far 5 subtypes of disease have been identified. Alteration of pro-survival, pro-proliferative and anti-apoptotic pathways including JAK/STAT, MAPK,
PI3K/AkT/mTOR, NF-κB, BCL2 and several others have induced oncogenic events including epithelial-mesenchymal transition, intra-vasation, extra-vasation and many more. Although several US-FDA approved drugs are available in market to target above mentioned signalling pathways but issues of resistance, side effects have restricted their efficacy. The present review article aims to highlight diverse molecular subtypes and the signalling pathways involved in complicating the disease along with the US-FDA approved drugs to target them. Potential herbal medicine to target the disease have also been emphasized that can be used either as mono-therapeutic approach or in combination with conventional therapeutic regimens to target breast cancer
Estimated Levels of Glycated Albumin and C-reactive Protein/Total Albumin Ratio might Distinguish Prediabetics among the Apparently Healthy People and Predict the Vulnerability for Development of Steatohepatitis and Cardiac Risk.
Background: Prediabetes precedes Type-2 diabetes development, is characterized by impaired glucose tolerance (IGT) as judged by the 75-gram oral glucose tolerance test (75-OGTT) and is associated with higher cardiac risk (CR), dyslipidemia, hepatosteatosis (HS) and cancer
Aims: The study aimed to determine the distinguishing ability of estimated levels of glycated albumin (GA) and hemoglobin A1c (HbA1c), and serum C-reactive protein (CRP) and serum total albumin (TA) levels for prediabetic out of apparently healthy subjects.
Methods: IGT was diagnosed if fasting blood glucose (FBG) was 100-125 mg/dl and if /dl subject is normal glucose tolerant (NGT). CR, HS and insulin resistance (IR) were suggested if the calculated atherogenic index of plasma (AIP) was \u3e0.1, HS index (HSI) was \u3e36 with high computerized hepatorenal index (HRI) and the homeostasis model assessment of IR (HOMA-IR) score was \u3e2, respectively.
Results: 253 subjects (50.8%) had IGT and were older, more obese and mainly females. IGT had higher GA%, HOMA-IR score, serum CRP and lower TA with high CRP/TA ratio (CAR) than NGT. The frequency of subjects had AIP\u3e0.1, HSI\u3e36 and high HRI was significantly higher among IGT subjects. Statistical analyses defined high GA% and CAR as predictors for IGT, HOMA-IR\u3e36 and AIP score \u3e0.1, while high CAR is the only predictor for HSI score \u3e36 and high HIR score
Conclusion: Prediabetes is not uncommon and high GA% and CAR might differentiate them among the apparently healthy population, and could predict those at increased risk for IR, HS and at C
Metabolomics in cancer detection: A review of techniques, biomarkers, and clinical utility
Cancer poses a significant burden on global public health, contributing to high mortality rates worldwide. Ongoing diagnostic strategies have predominantly relied on imaging techniques, histopathological examination and molecular analyses which have limitations in sensitivity, and specificity. Early cancer detection is a pivotal determinant of successful treatment and patient survival rates. Metabolomic applications involve the comprehensive analysis of metabolites to understand the metabolic profile of an organism, tissue, or cell under different conditions such as lack of oxygen in tumors. The aim of this review is to provide an extensive approach of metabolomic applications in early cancer detection and to provide an overview of the strengths and limitations of metabolomic approaches in early cancer detection. Metabolomic profiling can identify specific metabolic biomarkers indicative of early-stage cancer. The identification of these biomarkers can lead to development of non-invasive diagnostic tests which can be used for early cancer screening. Several researchers have already employed the metabolomics approach for biomarker discovery, diagnosis, identifying new drug targets along with the clinical trials observations. When discussing challenges, researchers currently face a notable obstacle, the absence of standardized analytical procedures. It is imperative for the field to prioritize implementing computational tools for constructing open-source databases, thereby advancing metabolomic studies in cancer researc
Tai Chi for Cardiovascular Wellness: Integrating an Ancient Practice into Modern Therapeutic Approaches
Tai Chi, a traditional Chinese martial art characterized by gentle, fluid movements and deep breathing, has gained increasing recognition for its cardiovascular health benefits. This study investigated the integration of Tai Chi into contemporary cardiovascular health practices, focusing on its physiological and psychological effects. The slow, controlled movements characteristic of Tai Chi contribute to enhanced cardiovascular fitness, decreased blood pressure, and improved vascular function, while simultaneously alleviating stress and fostering emotional well-being. Through a review of clinical studies and trials, this study underscores the efficacy of Tai Chi in cardiovascular rehabilitation programs and its accessibility as a community-based intervention. Additionally, this study addresses obstacles to widespread adoption, including cultural barriers and the lack of standardized training for instructors. By integrating traditional practices with contemporary medical approaches, Tai Chi is as a valuable complementary therapy for cardiovascular health. The paper presents future research directions and advocacy strategies aimed at promoting broader acceptance and implementation of Tai Chi in health-care settings. This review underscores the continued relevance of Tai Chi as an effective intervention for cardiovascular wellness in modern therapeutic contexts
From Rhythm to Resilience: The Interplay of Circadian Rhythm, Melatonin, Lifestyle, Nutrition in Psychoneuroimmunology (PNI)
Emerging evidence reveals that circadian rhythm, melatonin signaling, nutrition, and inflammation are intricately intertwined in shaping both mental and physical health. Circadian disruptions and lifestyle imbalances contribute to neuroinflammation, mood dysregulation, and cardiometabolic dysfunction, as seen in attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), metabolic syndrome,and cardiovascular diseases. This special issue highlights interdisciplinary research that integrates circadian biology, nutrition, and psychoneuroimmunology (PNI) toward personalized and preventive psychiatry. Featured studies explore circadian and melatonin mechanisms in ADHD and MDD, the therapeutic and prophylactic potential of omega-3 polyunsaturated fatty acids (n-3 PUFAs), the neuroprotective potentical of paeoniflorin, and the role of extracellular matrix gene variants in MDD vulnerability. Additionally, evidence supporting lifestyle-based interventions such as Tai Chi underscores the value of nonpharmacological mind–body approaches. Collectively, these studies illuminate a multidimensional model linking biological rhythm, nutrition, and inflammation to mental resilience and cardiovascular well-being
The Protective Role of Astaxanthin Against Oxidative Stress and Inflammation in Peritoneal Dialysis Rats
Background: Prolonged exposure of peritoneal membrane to dialysate solution is known to cause fibrosis mediated by imbalanced inflammatory response and oxidative stress. In this context, proinflammatory cytokines including TGF-β and IL-1β, along with oxidative stress markers namely SOD and MDA, present in circulation, could serve as indicators of fibrosis. This phenomenon has the potential to interfere with the optimization of Chronic Kidney Disease (CKD) treatment. Other oral antioxidant supplements have been widely studied to prevent peritoneal damage, but investigations regarding Astaxanthin (AST) effect on fibrosis marked with proinflammatory cytokine are still limited.
Aims: This study aimed to investigate the protective role of AST supplementation against fibrosis in peritoneal dialysis by evaluating proinflammatory cytokine levels.
Results: The results showed that AST supplementation reduced the levels of MDA, TGF-β, and IL-1β within the circulation while also improving SOD concentration in peritoneal dialysis-induced rats, as indicated by p \u3c 0.05.
Conclusion: This study found that AST supplementation might prevent peritoneal fibrosis by decreasing MDA, TGF-β, and IL-1β, as well as increasing SOD levels in serum
Cyclohexylamine, the principal metabolite of cyclamate, contracts the epididymal vas deferens of rats by affecting endogenous catecholamine release via postsynaptic α1Aand presynaptic α2-adrenoceptors in a calcium-dependent manner
Background: Cyclohexylamine (CHA) is a principal metabolite of cyclamate, which was once one of the most prominently consumed non-sugar sweeteners. Earlier studies suggested that long-term use of cyclamate might be carcinogenic and genotoxic; however, no consistent evidence supports an association between cyclamate and cancer risk. However, this issue remains interesting. Cyclamate can be metabolized to CHA by the intestinal bacteria in humans and some animals. Previous reports indicated CHA could induce atrophy of rat testes and affect rat fertility, as well as contract rat vas deferens. However, the contractile mechanisms of CHA on rat vas deferens remains poorly understood. This study investigated the contractile mechanisms of CHA on the isolated rat epididymal portion of the vas deferens.
Methods: Male S.D. rats weighing between 200 g and 250 g were used. The isolated epididymal portion of rat vas deferens was added to calcium-channel blockers, calcium-free conditions or various concentrations (1x10-8M-1x10-5M) of adrenergic antagonists and CHA (1x10-4M).
Results: CHA (1x10-5M-1x10-1M) evoked a concentration-dependent contraction. Calcium- channel blocker, nifedipine (1x10-8 M-1x10-6 M) or verapamil (1x10-8 M-1x10-5 M) pretreatment, dose-dependently attenuated the CHA (1x10-4 M)-induced contraction. The calcium-free condition completely blocked CHA (1x10-4 M)-induced contraction. Prazosin (1x10-8M-1x10-6M) or yohimbine (1x10-7 M-1x10-5 M) pretreatment or treatment could inhibit contractions evoked by CHA (1x10-4M) in a dose-dependent manner. Moreover, the effect of CHA(1x10-4 M) was entirely blocked by combining prazosin and yohimbine pretreatment. WB4101 (1x10-8M) could completely inhibit the contractions induced by CHA (1x10-4M). CEC (1x10-8M-1x10-4M) showed no significant inhibitory effect on the contractile tension but reduced the frequency induced by CHA (1x10-4M). Moreover, reserpine (1x10-5M) showed a significant inhibition on the contractions of CHA(1x10-4M).
Conclusions: The above results indicate CHA-contracts epididymal vas deferens by affecting endogenous catecholamine release via postsynaptic α1A- and presynaptic α2- adrenoceptors and are calcium-dependent.