Novel ibuprofen prodrug: A possible promising agent for the management of complications of Alzheimer's disease.

Background: Alzheimer's disease (AD) is a severe, varied, and complex brain condition that gradually impairs memory and cognitive function. Epidemiological studies have shown that patients who have a history of long-term NSAID use have a decreased risk of developing AD. The objective of this study is to conduct the structural analysis of a novel ibuprofen prodrug and test its anti-Alzheimer's properties. Methods: Computational and docking studies were conducted using AMBER 18 package. The in-vivo studies were performed using aluminum chloride-induced experimental AD in rats. Adult Wistar rats of either sex were used and treated with aluminum chloride (32.5 mg/kg, p.o) and ibuprofen prodrug (50 mg/kg, p.o) daily for 30 days. The hole-board test and elevated plus maze were conducted on 10th, 20th and 30th day. Further, on 31st day, animals were euthanized and the brain tissue was used for histopathology. The results obtained were subjected to statistical analysis by one-way ANOVA and Dunnet's test, p < 0.05 was considered to indicate the significance. Results: The structural configuration of the novel compound indicated the presence of several structures such as aliphatic, aromatic, and asymmetry in the compound. The geometrical analysis indicated that the ibuprofen conjugate has dreiding energy of 51.22 kcal/mol with a van der waals radius of 62.56 A. The Huckel analysis confirmed the presence of aromatic rings in the compound. The molecular docking studies suggested affinity towards beta-secretase and acetylcholinesterase, besides indicating that the compound has ideal characteristics for the oral route (Log P = 2.33), cellular absorption (TPSA = 95.50), and oral bioavailability (number of rotatable bonds = 10). The toxicity profile indicated devoid of major systemic toxicity with mild possibility of cytotoxicity. The in-vivo analysis showed that the Ibu-prodrug significantly (P < 0.001) reversed the changes induced by aluminum chloride and restored histomorphological features in brain tissue. Conclusion: The findings suggested that the ibuprofen conjugate might possess the potential to manage the complications of AD. The action appears to be mediated through inhibition of beta-secretase and acetylcholinesterase activities. More studies might aid in identifying a specific therapeutic intervention that is still lacking in the treatment of AD.

The Cardiac Comeback-Beating Stronger: Exploring the Remarkable Resilience of the Heart in COVID-19 Recovery through Cardiac Autonomic Analysis.

Background and Objectives: Analyzing the cardiac autonomic function in COVID-19 patients can provide insights into the impact of the virus on the heart's regulatory mechanisms and its recovery. The autonomic nervous system plays a crucial role in regulating the heart's functions, such as heart rate, blood pressure, and cardiac output. This study aimed to investigate the impact of COVID-19 on heart rate variability (HRV) during a 6-min walk test (6MWT). Materials and Methods: The study included 74 participants, consisting of 37 individuals who had recovered from mild to moderate COVID-19 and 37 healthy controls. The study assessed heart rate variability (HRV) and blood pressure both before and after a 6-min walk test (6MWT). Results: The study found significant differences in a few time domains (SDNN and pNN50) and all frequency domain measures, whereas there were no significant differences in demographic characteristics or blood pressure between COVID-19-recovered individuals and healthy controls at rest. There were significant 6MWT effects on average HR, time-domain (SDNN and pNN50) measures of HRV, and all frequency domain measures of HRV. A significant group × 6MWT interaction was found for SDNN, pNN50, total power, Ln total power, LF, HF, Ln LF, Ln HF, and LF nu. Conclusions: Cardiac Autonomic analysis through HRV is essential to ensure the continued health and well-being of COVID-19 survivors and to minimize the potential long-term impacts of the disease on their cardiovascular system. This suggests that HRV analysis during the recovery phase following exercise could serve as a valuable tool for evaluating the physiological effects of COVID-19 and monitoring the recovery process.

Pilot-Study to Explore Metabolic Signature of Type 2 Diabetes: A Pipeline of Tree-Based Machine Learning and Bioinformatics Techniques for Biomarkers Discovery.

BACKGROUND: This study aims to identify unique metabolomics biomarkers associated with Type 2 Diabetes (T2D) and develop an accurate diagnostics model using tree-based machine learning (ML) algorithms integrated with bioinformatics techniques. METHODS: Univariate and multivariate analyses such as fold change, a receiver operating characteristic curve (ROC), and Partial Least-Squares Discriminant Analysis (PLS-DA) were used to identify biomarker metabolites that showed significant concentration in T2D patients. Three tree-based algorithms [eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), and Adaptive Boosting (AdaBoost)] that demonstrated robustness in high-dimensional data analysis were used to create a diagnostic model for T2D. RESULTS: As a result of the biomarker discovery process validated with three different approaches, Pyruvate, D-Rhamnose, AMP, pipecolate, Tetradecenoic acid, Tetradecanoic acid, Dodecanediothioic acid, Prostaglandin E3/D3 (isobars), ADP and Hexadecenoic acid were determined as potential biomarkers for T2D. Our results showed that the XGBoost model [accuracy = 0.831, F1-score = 0.845, sensitivity = 0.882, specificity = 0.774, positive predictive value (PPV) = 0.811, negative-PV (NPV) = 0.857 and Area under the ROC curve (AUC) = 0.887] had the slight highest performance measures. CONCLUSIONS: ML integrated with bioinformatics techniques offers accurate and positive T2D candidate biomarker discovery. The XGBoost model can successfully distinguish T2D based on metabolites.

Clinicopathological Significance and Expression Pattern of Bcl2 in Breast Cancer: A Comprehensive in silico and in vitro Study.

B-cell lymphoma/leukemia gene-2 (Bcl-2) is the primary proto-oncogene that has been shown to work by preventing apoptosis/programmed cell death. Bcl-2 combines a variety of cell-generated signals associated to the survival and death of cells. In glioma, lung, and breast cancer, Bcl-2 over-expression has been linked to an increase in invasion and migration. Many treatment regimens that target Bcl2 have been established and approved, and thus increasing the survival rates of the patients. The primary goal of this research was to recognize new therapeutic compounds that target Bcl2 and assess Bcl2 expression pattern in BC patients. We used various bioinformatic tools as well as several in vitro assays to look out the expression and inhibition of Bcl2 in BC. Our study depicted that Bcl2 had a strong connection with tumour stroma, notably with suppressor cells originating from myeloid tissues. Moreover, in vitro and in silico research identified Paclitaxel as a promising natural substance that targets Bcl2. Overall, this work shows that Bcl2 overexpression accelerates the development of BC, and that targeting Bcl2 in combination with other drugs will dramatically improve BC patient's response to treatment and prevent the emergence of drug resistance.

Ferroptosis targeting natural compounds as a promising approach for developing potent liver cancer agents.

Liver cancer is the second leading cause of cancer-related death worldwide. However, treatment options, including surgical resection, transplantation, and molecular drug therapies, are of limited effectiveness. Recent studies have demonstrated that suppressing ferroptosis might be a pivotal signal for liver cancer initiation, thus providing a new way to combat liver cancer. Ferroptosis is a distinct form of controlled cell death that differs from conventional cell death routes like apoptosis, necrosis, and pyroptosis. It results from intracellular iron overload, which raises iron-dependent reactive oxygen species. This, in turn, leads to the accumulation of lipid peroxides that further result in oxidative damage to cell membranes, disrupt normal functioning, and ultimately speed up the ferroptosis phenomenon. Ferroptosis regulation is intricately linked to cellular physiological processes, encompassing iron metabolism, lipid metabolism, and the equilibrium between oxygen-free radical reactions and lipid peroxidation. This review intends to summarize the natural compounds targeting ferroptosis in liver cancer to offer new therapeutic ideas for liver cancer. Furthermore, it serves as the foundation for identifying and applying chemical medicines and natural chemicals that target ferroptosis to treat liver cancer efficiently.

Assessing muscle energy technique and foam roller self-myofascial release for low back pain management in two-wheeler riders.

Pain in the lower back is a major concern in today's era due to prolonged sitting in two-wheeler riders, mainly due to hamstring tightness. It also creates physical disability and impairment in activities of daily living. The study aimed to compare the efficacy of muscle energy technique (MET) and self-myofascial release (SMFR) using the foam roller on hamstring flexibility, dynamic balance, and physical disability amongst two-wheeler riders with chronic low back pain (LBP). Participants were randomized into two intervention groups, MET and SMFR using the envelope method, with each group having 20 participants. Hamstring flexibility and range of motion for knee extension and the lower back were assessed using the active knee extension test (AKE-L and AKE-R) and sit and reach test (SRT), while the dynamic balance was assessed by the star excursion balance test (SEBT) and physical disability by Roland-Morris Disability Questionnaire, (RMDQ). Measurements were taken at baseline and after 4 weeks of intervention. This study demonstrated that both SMFR using a foam roller and MET are effective in enhancing hamstring muscle flexibility, (SRT-F(1, 38) = 299.5, p < 0.001; AKE-R-F(1, 38) = 99.53, p < 0.001; AKE-L-F(1, 38) = 89.67, p < 0.001). Additionally, these techniques significantly improved dynamic balance in various directions, including anterior (ANT), anteromedial (AMED), medial (MED), posteromedial (PMED), posterior (POST), posterolateral (PLAT), lateral (LAT), and anterolateral (ALAT) directions (p < 0.01). Furthermore, there was a significant reduction in physical disability (RMDQ-F(1, 38) = 1307, p < 0.001), among two-wheeler riders suffering from chronic LBP. Compared to MET, SMFR using foam rollers was found to be more effective in enhancing hamstring flexibility, improving balance, and decreasing disability level on the RMDQ after 4 weeks.

Exploring the role of trifarotene against RAR-α: an investigation of expression pattern and clinicopathological significance of RAR-α in breast cancer.

Introduction: The members retinoic acid receptors (RARs) (α, ß, and γ) and retinoid X receptors (RXRs) (α, ß, and γ) belong to the retinoid receptor family. They regulate the biological action of classical retinoids through nuclear retinoid receptors, a transcription factor that is regulated by ligands. Through the binding of particular retinoic acid-responsive elements (RAREs) located in target gene promoters, RARs and members of the RXRs form heterodimers. By binding to its nuclear receptors and triggering the transcription of the target genes downstream, retinoic acid (RA) mediates the expression of certain genes. Retinoids so mainly control gene expression to carry out their biological actions. RARs are essential for many biological processes, such as development, immunity, reproduction, organogenesis, and homeostasis. Apart from their physiological functions, RARs are also linked to pathologies and tumors due to mutations, protein fusions, changes in expression levels, or abnormal post-translational changes that lead to aberrant functions and homeostasis breakdown. The oncogenic development of animal tissues or cultured cells is linked to altered expression of retinoid receptors. The RAR-α is over-expressed in several malignancies. Increased invasion and migration in several cancer forms, including HNSC carcinoma, pediatric low-grade gliomas, lung adenocarcinoma, and breast cancer, have been linked to its upregulated expression. Numerous approved therapeutic regimens targeting RAR-α have been developed, improving patient survival rates. Objective: This study's main objective was to identify novel RAR-α-targeting drugs and evaluate the expression patterns of RAR-α in breast cancer patients. Methodology: In-silico investigation using a variety of bioinformatics tools like UALCAN, TISCH, TIMER 2.0, ENRICHR, and others were employed to examine the expression of RAR-α. Further we evaluated in-silico inhibition of RAR-α with trifarotene and also tested the cytotoxicity of trifarotene in breast cancer cells. Results: Our research indicates that RAR-α is upregulated in several malignancies including Breast Cancer. It regulates granulocyte differentiation and has an association with the retinoic acid receptor signaling pathway and cellular response to estrogen stimulus. Furthermore, trifarotene was found as a potential synthetic compound that targets RAR-α through in silico and in-vitro study. Discussion: Overall, this research indicates that elevated expression of RAR-α enhances the onset of breast cancer. Using trifarotene medication to target RAR-α will significantly boost the response of breast cancer individuals to treatment and delay the development of resistance to drugs.

Exploring HMMR as a therapeutic frontier in breast cancer treatment, its interaction with various cell cycle genes, and targeting its overexpression through specific inhibitors.

Among women, breast carcinoma is one of the most complex cancers, with one of the highest death rates worldwide. There have been significant improvements in treatment methods, but its early detection still remains an issue to be resolved. This study explores the multifaceted function of hyaluronan-mediated motility receptor (HMMR) in breast cancer progression. HMMR's association with key cell cycle regulators (AURKA, TPX2, and CDK1) underscores its pivotal role in cancer initiation and advancement. HMMR's involvement in microtubule assembly and cellular interactions, both extracellularly and intracellularly, provides critical insights into its contribution to cancer cell processes. Elevated HMMR expression triggered by inflammatory signals correlates with unfavorable prognosis in breast cancer and various other malignancies. Therefore, recognizing HMMR as a promising therapeutic target, the study validates the overexpression of HMMR in breast cancer and various pan cancers and its correlation with certain proteins such as AURKA, TPX2, and CDK1 through online databases. Furthermore, the pathways associated with HMMR were explored using pathway enrichment analysis, such as Gene Ontology, offering a foundation for the development of effective strategies in breast cancer treatment. The study further highlights compounds capable of inhibiting certain pathways, which, in turn, would inhibit the upregulation of HMMR in breast cancer. The results were further validated via MD simulations in addition to molecular docking to explore protein-protein/ligand interaction. Consequently, these findings imply that HMMR could play a pivotal role as a crucial oncogenic regulator, highlighting its potential as a promising target for the therapeutic intervention of breast carcinoma.

Computational investigation of 2, 4-Di Tert Butyl Phenol as alpha amylase inhibitor isolated from Coccinia grandis (L.) Voigt using molecular docking, and ADMET parameters.

INTRODUCTION: Diabetes Mellitus is the metabolic disorder most prevalent globally, accounting for a substantial morbidity rate. The conventional drugs available for the management of diabetes are either expensive or lack the required efficacy. The purpose of this research is to isolate and characterize an active phytoconstituent from Coccinia grandis and assess its anti-diabetic properties. METHODS AND MATERIALS: Stems of Coccinia grandis are subjected to successive extraction and isolation. The isolated compound by column chromatography was characterized by FTIR (fourier-transform infrared), 1 H NMR (proton nuclear magnetic resonance), and Mass spectroscopy. The antidiabetic potential of the isolated compound was evaluated by in-vitro alpha-amylase inhibitory activity. Further, the compound was subjected to molecular docking studies to study its interaction with the human pancreatic alpha-amylase (Molegro Virtual Docker) as well to determine the pharmacokinetic and toxicity profile using computational techniques (OSIRIS property explorer, Swiss ADME, pkCSM, and PreADMET). RESULTS: The characterization of the compound suggests the structure to be 2,4-ditertiary butyl phenol. The in-vitro alpha-amylase inhibitory study indicated a concentration-dependent inhibition and the IC50 (median lethal dose) value of the isolated compound was found to be 64.36 µg/ml. The docking study with the A chain of receptor 5EMY yielded a favorable docking score of -81.48 Kcal mol-1, suggesting that the compound binds to the receptor with high affinity through electrostatic, hydrophobic, and hydrogen bonds. Furthermore, the silico ADME analysis of the compound revealed improved metabolism, a skin permeability of -3.87 cm/s, gastrointestinal absorption of 95.48 %, and a total clearance of 0.984 log ml min-1 kg-1. In silico toxicity analysis also predicted cutaneous irritations but no carcinogenicity, mutagenicity, or hepatotoxicity. CONCLUSION: The data suggested that the isolated compound (2, 4-tertiary butyl phenol) has the potential to inhibit the alpha-amylase activity and possess optimal ADME properties as well as tolerable side effects.

Mesenchymal stem cells and their potential therapeutic benefits and challenges in the treatment and pathogenesis of gastric cancer.

Mesenchymal stem/stromal cells (MSCs) are acknowledged for their remarkable ability to undergo differentiation into various cell types. In addition, they exhibit anti-tumor characteristics, prompting endeavors to modify MSCs for employment in cancer therapies. On the contrary, it is imperative to recognize that MSCs have been extensively linked to pathways that facilitate the advancement of tumors. Numerous research studies have sought to modify MSCs for clinical application; however, the outcomes have been ambiguous, potentially due to the heterogeneity of MSC populations. Furthermore, the conflicting roles of MSCs in suppressing and promoting tumor growth present a challenge to the appropriateness of their use in anti-cancer therapies. Currently, there exists a lack of comprehensive comprehension concerning the anti-tumor and pro-tumor characteristics of MSCs for gastric cancer (GC). This article discusses the influence of MSCs on GC, the underlying mechanisms, the origins of MSCs, and their effects. This review article also elucidates how MSCs exhibit dual characteristics of promoting and inhibiting tumor growth. Hence, it is of utmost importance that clinical inquiries aimed at utilizing MSCs as a therapeutic intervention for cancer consider the potentiality of MSCs to accelerate the progression of GC. It is crucial to exercise caution throughout the process of developing MSC-based cellular therapies to enhance their anti-cancer attributes while simultaneously eliminating their tumor-promoting impacts.

Metabolic effects of a submaximal dose of pink salt and monosodium glutamate in experimental rats.

Background & objectives: Pink salt and monosodium glutamate (MSG) are two typical food additives used in cooking to enhance flavour. However, excessive use of them has been associated to a variety of metabolic problems, including weight gain and hyperglycemia. The current study aimed to assess the metabolic changes caused by submaximal dosages of MSG and pink salt in experimental rats. Methods: Twenty-four 120-150 g Wister rats of both sexes were divided into three groups: control, pink salt-treated (0.8 g/kg daily for three weeks), and MSG-treated (3.6 g/kg daily for three weeks). The body weight, amount of food and water consumed, and blood glucose levels of animals were measured and recorded as indicators of their metabolic changes. Furthermore, after salt treatments at intervals such as week 1, week 2, and week 3, the survival rate and general toxicity manifestations were determined. The results were statistically analysed using one-way ANOVA, with p < 0.05 being considered significant. Results: The study found that the group given a submaximal dose of MSG gained significantly more weight (p < 0.05), consumed more food and water, and had higher blood glucose levels than the control. Ninety percent of the MSG therapy group survived by the end of the third week, however, they suffered from negative effects like abdominal distention, respiratory problems, ptosis, and subcutaneous swelling. On the other hand, the consumption of food and drink was significantly (p < 0.05) increased upon the administration of pink salt. Only little changes were observed in the body weight, blood sugar levels, and general features (such as subcutaneous swelling, change in bowel colour, and loose stools). Additionally, it was shown that the survival rate remained unchanged, particularly after week 3. Conclusion: According to study findings, MSG may induce metabolic issues, increasing the chance of death. While there was no discernible metabolic aberration linked to pink salt. Further research is required to fully understand the mechanism and consequences of these taste enhancers on the host system before pink salt can be deemed safe.

Application of mesenchymal stem cells derived from the umbilical cord or Wharton's jelly and their extracellular vesicles in the treatment of various diseases.

Mesenchymal stem cells (MSCs) originating from the umbilical cord (UC) or Wharton's jelly (WJ) have attracted substantial interest due to their potential to augment therapeutic approaches for a wide range of disorders. These cells demonstrate a wide range of capabilities in the process of differentiating into a multitude of cell types. Additionally, they possess a significant capacity for proliferation and are conveniently accessible. Furthermore, they possess a status of being immune-privileged, exhibit minimal tumorigenic characteristics, and raise minimal ethical concerns. Consequently, they are well-suited candidates for tissue regeneration and the treatment of diseases. Additionally, UC-derived MSCs offer a substantial yield compared to other sources. The therapeutic effects of these MSCs are closely associated with the release of nanosized extracellular vesicles (EVs), including exosomes and microvesicles (MVs), containing lipids, microRNAs, and proteins that facilitate intercellular communication. Due to their reduced tumorigenic and immunogenic characteristics, in addition to their convenient manipulability, EVs have arisen as a viable alternative for the management of disorders. The favorable characteristics of UC-MSCs or WJ-MSCs and their EVs have generated significant attention in clinical investigations encompassing diverse pathologies. Therefore, we present a review encompassing current preclinical and clinical investigations, examining the implications of UC-MSCs in diverse diseases, including those affecting bone, cartilage, skin, liver, kidney, neural, lung, cardiovascular, muscle, and retinal tissues, as well as conditions like cancer, diabetes, sepsis, and others.

Investigating the Potential Therapeutic Mechanisms of Puerarin in Neurological Diseases.

Plants and their derived phytochemicals have a long history of treating a wide range of illnesses for several decades. They are believed to be the origin of a diverse array of medicinal compounds. One of the compounds found in kudzu root is puerarin, a isoflavone glycoside commonly used as an alternative medicine to treat various diseases. From a biological perspective, puerarin can be described as a white needle crystal with the chemical name of 7-hydroxy-3-(4-hydroxyphenyl)-1-benzopyran-4-one-8-D-glucopyranoside. Besides, puerarin is sparingly soluble in water and produces no color or light yellow solution. Multiple experimental and clinical studies have confirmed the significant therapeutic effects of puerarin. These effects span a wide range of pharmacological effects, including neuroprotection, hepatoprotection, cardioprotection, immunomodulation, anticancer properties, anti-diabetic properties, anti-osteoporosis properties, and more. Puerarin achieves these effects by interacting with various cellular and molecular pathways, such as MAPK, AMPK, NF-κB, mTOR, ß-catenin, and PKB/Akt, as well as different receptors, enzymes, and growth factors. The current review highlights the molecular mechanism of puerarin as a neuroprotective agent in the treatment of various neurodegenerative and neurological diseases. Extensive cellular, animal, and clinical research has provided valuable insights into its effectiveness in conditions such as Alzheimer's disease, Parkinson's disease, epilepsy, cerebral stroke, depression, and more.

Unveiling the impact of aging on BBB and Alzheimer's disease: Factors and therapeutic implications.

Alzheimer's disease (AD) is a highly prevalent neurodegenerative condition that has devastating effects on individuals, often resulting in dementia. AD is primarily defined by the presence of extracellular plaques containing insoluble ß-amyloid peptide (Aß) and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein (P-tau). In addition, individuals afflicted by these age-related illnesses experience a diminished state of health, which places significant financial strain on their loved ones. Several risk factors play a significant role in the development of AD. These factors include genetics, diet, smoking, certain diseases (such as cerebrovascular diseases, obesity, hypertension, and dyslipidemia), age, and alcohol consumption. Age-related factors are key contributors to the development of vascular-based neurodegenerative diseases such as AD. In general, the process of aging can lead to changes in the immune system's responses and can also initiate inflammation in the brain. The chronic inflammation and the inflammatory mediators found in the brain play a crucial role in the dysfunction of the blood-brain barrier (BBB). Furthermore, maintaining BBB integrity is of utmost importance in preventing a wide range of neurological disorders. Therefore, in this review, we discussed the role of age and its related factors in the breakdown of the blood-brain barrier and the development of AD. We also discussed the importance of different compounds, such as those with anti-aging properties, and other compounds that can help maintain the integrity of the blood-brain barrier in the prevention of AD. This review builds a strong correlation between age-related factors, degradation of the BBB, and its impact on AD.

Age-Related Decline in Cervical Proprioception and Its Correlation with Functional Mobility and Limits of Stability Assessed Using Computerized Posturography: A Cross-Sectional Study Comparing Older (65+ Years) and Younger Adults.

Cervical proprioception and its implications on postural stability are crucial in older adults. Understanding their relationship is important in understanding and preventing falls in older adults. This research aims to evaluate the proprioceptive, functional mobility, and limits of stability (LOS) variables among two age groups: individuals aged 65 and above and those below 65. A secondary goal of the study is to analyze the relationship between cervical proprioception, functional mobility, and the LOS. METHODS: In this cross-sectional study, 100 participants each were included in the older and younger groups. Researchers employed the target reposition technique to assess cervical proprioception and measured the joint position error (JPE) in degrees. Functional mobility was estimated using the Berg balance scale (BBS) and timed up-and-go test (TUG). In addition, dynamic posturography was utilized to evaluate variables related to the LOS, including reaction time, maximum excursion, and directional control. RESULTS: The magnitudes of the mean cervical JPE are larger (p < 0.001), and functional mobility (p < 0.001) and the LOS (p < 0.001) are impaired in older individuals compared to the younger ones. The cervical proprioception is significantly associated with functional mobility (p < 0.001), and the LOS (p < 0.001). CONCLUSION: In older adults aged above 65 years, cervical proprioception, functional mobility, and the LOS are impaired. Older adults with greater cervical JPE had more impaired functional mobility and LOS parameters. When evaluating or treating older adults with problems with their balance or falls, these factors should be considered.

Exploring the impact of integrated polyvagal exercises and knee reinforcement in females with grade II knee osteoarthritis: a randomized controlled trial.

This study aimed to compare the effects of knee strengthening exercises to those of polyvagal theory-based exercises combined with knee strengthening exercises on selected outcomes in women with grade II knee osteoarthritis (OA). A randomized controlled trial was conducted, in which 60 female participants diagnosed with grade II knee OA, with a mean age of 57.27 ± 7.81 years and knee pain rated between 4 and 7 on the visual analog scale (VAS), were assigned to either the knee strengthening exercise group (Group 1, n = 30) or the polyvagal theory-based exercise plus knee strengthening exercise group (Group 2, n = 30). Pre- and posttreatment assessment of outcome variables, including WOMAC scores (joint pain, joint stiffness, functional limitations, and the overall index), WHOQOL scores (overall quality of life, general health, physical, psychological, social, and environmental domains), and heart rate variability (HRV, time and frequency domains), were analyzed. Group 2 demonstrated significantly greater reductions in joint pain, stiffness, and functional limitations than Group 1 after the intervention. Group 2 presented with significantly improved WOMAC scores, indicating better overall outcomes. Group 2 showed significant improvements in the psychological and social domains regarding quality of life. There were no significant differences in the physical domain or the environmental domain. Group 2 showed a significant increase in high-frequency power (HF) and a significant decrease in the LF/HF ratio, suggesting improved autonomic regulation. A combination of polyvagal exercise and knee strengthening training resulted in superior outcomes compared to knee strengthening exercises alone in women with grade II knee OA. These findings support the potential effectiveness of incorporating polyvagal exercises as an adjunctive intervention for osteoarthritis management.

Targeting p53 misfolding conundrum by stabilizing agents and their analogs in breast cancer therapy: a comprehensive computational analysis.

Cancer continues to be a major global public health concern and one of the foremost causes of death. Delays in the diagnosis and cure may cause an increase in advanced stage disease and mortality. The most common cancer found in women currently is breast carcinoma. Breast carcinoma has surpassed lung carcinoma and currently represents the chief type of cancer diagnosed (2.3 million new cases, which amount to 11.7% of all cancer cases). In addition, by 2040, the incidence will increase by more than 46% as per the estimates of GLOBOCAN. Triple-negative breast cancer (TNBC) represents a highly aggressive and invasive subtype of breast cancer, characterized by rapid progression, short response time to the available treatment, and poor clinical results. Thus, it is very crucial to develop novel diagnostic tools and therapeutics with good efficacy. A majority of cancers display malfunction along the p53 pathway. Moreover, p53 not only loses its function but is also prone to misfolding and aggregation, leading to formation of amyloid aggregates as well. Research is being carried out to find ways to restore the normal action and expression of p53. Here, we have explored PhiKan-083 for its possible stabilizing effect on p53 in order to address the problem with its misfolding. Thus, examining the analogs of PhiKan-083 that have a role in p53 stability will help update our understanding of cancer progression and may expedite the progress of new anticancer treatments. We anticipate that the drug molecules and their analogs targeting p53 aggregation may be used in combination with other anticancer compounds to solve the problem with p53 aggregation. In this study, by employing ADMET analysis, the compounds were screened, and we further examined the chosen compounds with the help of molecular docking. By using databases like UALCAN, TIMER, GEPIA, and PredictProtein, we investigated TP53's expression pattern and prognostic relevance in various cancer settings.

Enhancing Functional Ability in Chronic Nonspecific Lower Back Pain: The Impact of EMG-Guided Trunk Stabilization Exercises.

BACKGROUND: Nonspecific lower back pain (NSLBP) is described as pain that is not caused by an identifiable, well-known disease, such as infection, tumor, osteoporosis, fracture, structural deformity, inflammatory condition, radicular syndrome, or cauda equina syndrome. AIM: The aim of this study was to determine the effect of EMG-guided trunk stabilization exercises on functional disability associated with LBP. MATERIALS AND METHODS: A single-blinded pre- and post-test experimental comparative design was used for this study. Fifty individuals with chronic NSLBP were screened for inclusion criteria. Of these, forty were randomly grouped into the EMG group receiving trunk-stability exercises with electromyography biofeedback and non-EMG group receiving trunk-stabilization exercises without EMG biofeedback. Participants performed five trunk-stability exercises 3 days a week for 4 weeks. The intensity of pain, range of motion, functional disability, and balance were measured at baseline and after 4 weeks. RESULTS: Both techniques indicated a significant effect on chronic NSLBP; however, trunk-stability exercises combined with EMG biofeedback produced better results in alleviating the intensity of pain, increasing the range of motion, and improving functional disabilities and static balance. CONCLUSION: The present study confirms that trunk-stability exercises with EMG biofeedback can be practiced safely, contributes to a greater boost in neuromuscular efficiency in the lumbar flexors and extensors, and is effective in modifying functional disability for patients with NSLBP.

Influence of Joint Flexibility, Hand Grip Strength and Pain on Oral Hygiene in Musculoskeletal Disorders-A Non-Interventional Clinical Study.

Diseases of the oral cavity and musculoskeletal disorders (MSDs) are common occurrences. They are commonly linked with partial mobility, resulting in limited visits to dentists for routine oral care, causing poor periodontal condition, bleeding, gingival inflammation, and increased depth of periodontal pockets. The present study was conducted to measure joint movements, hand grip strength, and pain in joints and their association with oral health. MATERIALS AND METHODS: The study included 200 subjects, half suffering from back, neck, shoulder, elbow, and wrist problems, belonging to different age groups and professions; 100 had joint pain, and 100 were without joint pain. The study assessed individuals exposed to oral health issues by measuring the strength of hand grip, flexibility, and pain score of the back, neck, shoulder, elbow, and wrist. The strength of the hand grip and the angle of the elbow and shoulder were measured in addition to a questionnaire to assess the relationship between back pain and oral health. To evaluate dental health status and oral hygiene, the total number of decayed, missing, and filled teeth (DMF/T) and Oral Hygiene Index-Simplified (OHI-S) indices were used. RESULTS: The difference between all demographic parameters was statistically significant (p < 0.05). It was observed that there was a significant difference in calculus, debris, and dental caries scores in both groups, with significantly lower scores and better oral hygiene in patients without joint pain. Concerning pain score and joint movements, the group without joint pain showed a significantly better range of movements and less pain than patients suffering from joint pain, and statistically a significant difference (p < 0.05) was observed between both groups. CONCLUSION: The present study revealed that musculoskeletal disorders, pain in the neck and hand, and restricted movements were common among professionals. We observed that pain in joints, neck, and hands, with restricted movements, caused a serious impact on the maintenance of oral hygiene practices among subjects of different professions.