International journal of physiology, pathophysiology and pharmacology最新文献

Background: Type 2 diabetes mellitus (T2DM) increases the risk of fractures. This meta-analysis compared the effects of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) on fracture risk in patients with T2DM.

Method: A systematic search of PubMed, Web of Science, Embase, and Google Scholar was conducted up to August 6, 2023. Seven cohort studies (n = 1,199,267 participants at baseline; n = 357,119 after propensity matching) comparing SGLT-2i use with DPP-4i use and reporting fracture outcomes were included. Data were extracted and analyzed using a random-effects model. Subgroup analyses were performed by age (<70 and ≥70 years) and sex.

Results: In general, SGLT-2i therapy was linked to reduced fracture risk when compared to DPP-4i (OR: 0.89, 95% CI: 0.81-0.98). Heterogeneity was high (I² = 64.3%). Upon stratified analysis by age, no statistically significant difference was observed between the fracture risk in the <70 years and ≥70 years subgroups upon comparison of SGLT-2i with DPP-4i. No significant difference was also observed in the female subgroup.

Conclusion: This meta-analysis indicates SGLT-2i therapy could be linked with reduced overall fracture risk in comparison to DPP-4i in the general population of T2DM. The benefit was not seen in subgroup analysis based on age and sex. Additional research, ideally with increased cases within subgroups, is required to determine the impact of these drugs on fracture risk in patient subgroups.

Background: "Laterality", or "lateral preference" indicates how differently or rather 'differentially' one tends to use a pair of sense organs or limbs. The most widely studied aspect of laterality is handedness. However, research on footedness has not received the same level of attention. Previous studies primarily relied on questionnaires to determine limb dominance, which may not provide the most accurate assessments. The present study aims to generate reliable objective data regarding both upper and lower limb dominance by analyzing surface electromyography (sEMG) parameters. Additionally, it seeks to correlate these findings with perceived limb dominance as indicated by questionnaire responses.

Methods and material: It was a cross-sectional observational study. The physiological parameters were recorded in the Clinical Physiology Laboratory. 20 male, healthy participants of 19-20 years participated in the study voluntarily. After recording of their demographic data, the study participants were assessed twice to ascertain the dominance of both upper and lower limbs. At first, they responded to the study questionnaires to report self-determined dominance of upper and lower limbs. Following this, the performance of both upper and lower limbs was evaluated by recording of surface EMG of specific muscles of the limbs at rest and during sustained contraction using a pre-defined load till the onset of fatigue. On the basis of normality test, the data were expressed as median with interquartile range. Wilcoxon signed rank test was performed to compare the parameters of sEMG. SPSS software version 20.0 (IBM Inc., USA) was used to analyse the data. A two-tailed P value less than 0.05 was taken as the cut-off level of significance.

Results: Based on questionnaire analysis, out of 20 participants, one was left-handed and the rest were right-handed. Six participants were found to use both legs and the rest were right leg dominant. Following analysis, no significant difference between the parameters of surface EMG (sEMG) of the corresponding muscles of the two upper and lower limbs was found. Even no significant difference between the time to set fatigue in right and left upper and lower limbs was observed.

Conclusions: The result of the present study indicates that the dominant and the non-dominant limbs have attained differences in such a manner that it has not affected their performances significantly. However, their different, though sometimes overlapping aspects of motion and movements is helpful for the performance of a given task.

Radiopharmaceutical therapy (RPT) is an advanced targeted cancer treatment that delivers radiation through specialized radiolabeled compounds to selectively destroy cancer cells while minimizing damage to healthy tissues. This theranostic approach integrates diagnosis and therapy, enhancing treatment precision and improving the therapeutic index compared to conventional chemotherapy. RPT agents consist of a radioactive isotope conjugated to a targeting molecule, enabling specific binding to cancer-associated antigens or receptors. Upon binding, these agents induce cell death through DNA damage caused by ionizing radiation. The choice of radionuclide, including beta and alpha emitters, plays a crucial role in determining therapeutic efficacy and potential side effects. This study aims to provide a comprehensive analysis of RPT, focusing on its mechanisms of action, clinical applications, and emerging challenges. We discuss the therapeutic potential of various radionuclides and highlight key clinical trials demonstrating efficacy across different malignancies. Additionally, we address critical issues such as optimizing delivery systems, managing radiotoxicity, and refining the dose-response relationship. Future directions include the development of novel radiopharmaceuticals and personalized treatment approaches. Further investigation is essential to overcome existing limitations and maximize the clinical benefits of RPT for patients with advanced cancers. Our findings contribute to a deeper understanding of RPT and offer insights into strategies for improving therapeutic outcomes and patient care.

Ayurveda, a traditional Indian medical system, offers a comprehensive approach to health promotion, disease prevention, and body rejuvenation, emphasizing wellness, vitality, and holistic well-being. Triphala, a well-established polyherbal Ayurvedic formulation, comprises equal proportions of Emblica officinalis (Amalaki or Amla), Terminalia bellerica (Bibhitaki or Bahera), and Terminalia chebula (Haritaki or Harad), demonstrating exceptional efficacy in gastrointestinal health and rejuvenation therapy. Triphala Rasayana, a polyherbal formulation, has been employed in Ayurveda, Siddha, and Unani medicine systems to address various health conditions. Its medicinal attributes include antioxidant, anticancer, antidiabetic, antimicrobial, immunomodulatory, and anticataract properties, making it a vital component in gastrointestinal treatment, particularly for functional gastrointestinal disorders. With its rich history in Ayurveda, Triphala's unique tridoshic properties harmonize the body's three essential energies - Vata, Pitta, and Kapha - fostering overall well-being and diverse health applications. The phytochemical composition of Triphala Rasayana is scrutinized, revealing essential bioactive compounds like phenolic acids, tannins, and flavonoids, which contribute to its antioxidant, anti-inflammatory, and antimicrobial effects. The therapeutic properties of Triphala span antidiabetic, hepatoprotective, and immunomodulatory effects, underpinned by studies demonstrating its benefits for oxidative stress, metabolic disorders, and immune enhancement. The review also underscores Triphala's role in gastrointestinal health, promoting beneficial microbiota and alleviating digestive issues, alongside its cardioprotective effects. Concluding with a call for advanced research into its pharmacodynamics and molecular mechanisms, the document advocates for integrating this potent Ayurvedic remedy into modern therapeutic regimens.

Lung cancer remains a leading cause of cancer-related mortality worldwide, and early detection is essential for improving patient outcomes. This study evaluates the role of artificial intelligence (AI) in lung nodule detection, focusing on its potential to enhance the accuracy of early lung cancer diagnosis. We assess the performance of AI tools, particularly convolutional neural networks (CNNs), in identifying and segmenting lung nodules from computed tomography (CT) and X-ray images. Our findings indicate that AI systems achieve a sensitivity of 70-90%, comparable to that of experienced radiologists, while reducing false-positive rates. In pulmonary nodule detection on CT scans, AI demonstrated over 95% sensitivity with fewer than one false-positive per scan. The implementation of AI as a "second reader" significantly improved detection accuracy. Despite these advancements, challenges remain, including high false-positive rates, issues with generalizability across diverse populations, regulatory concerns, and skepticism among healthcare professionals. This study highlights the promise of AI in supporting radiologists and improving lung cancer screening while emphasizing the need for further research to enhance specificity and address existing limitations.

Atrial fibrillation (AF) is the most prevalent arrhythmia, significantly increasing the risk of stroke and thromboembolism. Oral anticoagulants (OACs), including direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs), have been shown to reduce these risks effectively. However, the administration of OACs carries a notable risk of spontaneous intracranial hemorrhage (ICH), a severe complication associated with high morbidity and mortality. Patients with a history of ICH face a complex decision regarding the resumption of anticoagulation therapy, as the likelihood of recurrence is heightened in this population. Current literature reveals inconsistencies in research findings regarding the safety and efficacy of restarting OACs after ICH. A lack of definitive guidelines addressing this issue leaves clinicians uncertain about optimal management strategies. This systematic review aims to analyze existing observational studies and randomized controlled trials (RCTs) to evaluate the safety and effectiveness of resuming OACs in patients with AF who have experienced ICH. The review underscores the urgent need for high-quality research to inform clinical practices and develop comprehensive guidelines for managing anticoagulation therapy in this vulnerable group.

Objectives: The significant correlation between acute myocardial infarction and subsequent hepatorenal dysfunction could result in a higher mortality rate in patients. The study aimed to evaluate the effect and mechanisms of coenzyme-Q10 (Q10) administration on hepatorenal dysfunction in an isoprenaline (ISO)-induced myocardial infarction model in rats.

Materials and methods: Twenty male rats were assigned into four groups (n = 5). Groups 1-2 were administered intraperitoneally with normal saline, groups 3-4 were pretreated with Q10 (10 mg/kg, i.p.) for 28 days, and groups 2 and 4 received ISO (200 mg/kg, i.p.) on the last two days. Body, kidney, and liver weights, antioxidants and biochemical biomarkers, and histopathological investigation of the liver and kidney tissues were performed.

Results: The administration of ISO significantly (P < 0.05) increased oxidative stress and altered the liver and renal function integrity and morphology. Pretreatment with Q10 demonstrated a protective effect against biochemical and histological alterations through significantly enhanced antioxidant actions, notably increasing the levels of superoxide dismutase, catalase, glutathione, and glutathione transferase; reduced liver enzymes (aspartate transaminase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase), decreased urea and creatinine concentrations and reduced the gravity of histomorphological changes in hepatic and renal tissues of ISO treated rats.

Conclusion: Overall, our result suggests that Q10 confers hepatic and renal protection against ISO-induced hepatorenal dysfunction accompanying myocardial infarction through its antioxidant effects and amelioration of fibrotic changes.

Objective: The Heat Shock Protein 70 (HSP70) family is a highly conserved group of molecular chaperones essential for maintaining cellular homeostasis. These proteins are necessary for protein folding, assembly, and degradation and involve cell recovery from stress conditions. HSP70 proteins are upregulated in response to heat shock, oxidative stress, and pathogenic infections. Their primary role is preventing protein aggregation, refolding misfolded proteins, and targeted degradation of irreparably damaged proteins. Given their involvement in fundamental cellular processes and stress responses, HSP70 proteins are critical for cell survival and modulating disease outcomes in cancer, neurodegeneration, and other pathologies. The present study aims to understand domain architecture, physicochemical properties, phosphorylation, ubiquitination, and alternative polyadenylation site prediction in various HSP70 members.

Method: SMART and InterProScan software were used for domain analysis. EXPASY Protparam, NetPhos 3.1 server DTU, and MUbisiDa were used for physicochemical analysis, phosphorylation, and ubiquitination site analysis, respectively. Alternative polyadenylation was studied using the EST database.

Result: Domain analysis shows that coiled-coil and nucleotide-binding domains are present in some of the HSP70 members. Five HSP70 family members have alternate polyadenylation sites in their 3'UTR.

Conclusion: The present work has provided valuable insights into their structure, functions, interactome, and polyadenylation patterns. Studying their therapeutic potential in diseases like cancer can be helpful.

Metabolic syndrome is a group of pathological disorders increasing the risk of serious diseases including cardiovascular disease, stroke, type 2 diabetes. Global widespread of the metabolic syndrome has put a heavy social burden. Interestingly, a crucial link between the metabolic syndrome and a psychiatric disorder may frequently coexist, in which certain shared mechanisms might play a role for the pathogenesis. In fact, some microRNAs (miRNAs) have been detected in the overlap pathology, suggesting a common molecular mechanism for the development of both disorders. Subsequent studies have revealed that these miRNAs and several metabolites of gut microbiota such as short chain fatty acids (SCFAs) might be involved in the development of both disorders, in which the association between gut and brain might play key roles with engram memory for the modulation of immune cells. Additionally, the correlation between brain and immunity might also influence the development of several diseases/disorders including metabolic syndrome. Brain could possess several inflammatory responses as an information of pathological images termed engrams. In other words, preservation of the engram memory might be achieved by a meta-plasticity mechanism that shapes the alteration of neuron linkages for the development of immune-related diseases. Therefore, it might be rational that metabolic syndrome and psychiatric disorders may belong to a group of immune-related diseases. Disrupting in gut microbiota may threaten the body homeostasis, leading to initiate a cascade of health problems. This concept may contribute to the development of superior therapeutic application with the usage of some functional components in food against metabolic and psychiatric disorders. This paper reviews advances in understanding the regulatory mechanisms of miRNAs with the impact to gut, liver and brain, deliberating the probable therapeutic techniques against these disorders.

Alzheimer's disease is the most general type of cognitive impairments. Until recently, strategies that prevent its clinical progression have remained more elusive. Consequently, research direction should be for finding effective neuroprotective agents. It has been suggested oxidative stress, mitochondrial injury, and inflammation level might lead to brain cell death in many neurological disorders. Therefore, several autophagy-targeted bioactive compounds may be promising candidate therapeutics for the prevention of brain cell damage. Interestingly, some risk genes to Alzheimer's disease are expressed within brain cells, which may be linked to cholesterol metabolism, lipid transport, endocytosis, exocytosis and/or caveolae formation, suggesting that caveolae may be a fruitful therapeutic target to improve cognitive impairments. This review would highlight the latest advances in therapeutic technologies to improve the treatment of Alzheimer's disease. In particular, a paradigm that serotonin and N-methyl-d-aspartate (NMDA) receptors agonist/antagonist within caveolae structure might possibly improve the cognitive impairment. Consequently, cellular membrane biophysics should improve our understanding of the pathology of the cognitive dysfunction associated with Alzheimer's disease. Here, this research direction for the purpose of therapy may open the potential to move a clinical care toward disease-modifying treatment strategies with certain benefits for patients.