Elevated Levels Research Articles

The Role of Bile Acids in Pancreatic Cancer.

Bile acids are well known to promote the digestion and absorption of fat, and at the same time, they play an important role in lipid and glucose metabolism. More studies have found that bile acids such as ursodeoxycholic acid also have anti-inflammatory and immune-regulating effects. Bile acids have been extensively studied in biliary and intestinal tumors but less in pancreatic cancer. Patients with pancreatic cancer, especially pancreatic head cancer, are often accompanied by biliary obstruction and elevated bile acids caused by tumors. Elevated total bile acid levels in pancreatic cancer patients usually have a poor prognosis. There has been controversy over whether elevated bile acids are harmful or beneficial to pancreatic cancer. Still, there is no doubt that bile acids are important for the occurrence and development of pancreatic cancer. This article summarizes the research on bile acid as a biomarker and regulation of the occurrence, development and chemoresistance of pancreatic cancer, hoping to provide some inspiration for future research.

In-silico Assessment of Polyherbal Oils as Anti-diabetic Therapeutics.

Diabetes mellitus (DM) is characterized by elevated blood glucose levels either due to insufficient insulin production, defective insulin action, or both. It affects nearly 537 million individuals worldwide. Pharmacological treatment involves the use of oral antidiabetic agents as mono or combination therapy that effectively aids in controlling hyperglycemia. Despite providing therapeutic benefits, these medications limit their use owing to adverse side effects. Certain natural products, including essential oils, have promising anti-diabetic properties. The present study explores the effectiveness of two polyherbal oils and their compound towards the treatment of DM based on an In-silico approach to drug investigations Methods: Compounds present in the polyherbal oil formulation were identified using GCMS/ MS analysis. Selected compounds undergo molecular docking with the receptor, and proteins play an important role in DM. The potential compounds showing higher interactions than the known inhibitors or inducers were evaluated using molecular dynamic simulations RMSD value. The compounds identified through GC-MS analysis possess anti-diabetic and antiinflammatory properties. With the aid of in silico prediction methods, compounds such as geraniol, cinnamaldehyde, anethole, caryophyllene, terpinyl acetate, cymene, linalool, menthol, Phenol,2-methoxy-3-(2-propenyl), and 2,6- octadienal,3,7-dimethyl were identified as strong binders of GLUT4 and insulin receptor proteins. Geraniol and Phenol,2-methoxy-3-(2-propenyl) interaction with GLUT4 were of particular importance owing to their conformational stability. Our data suggest an agonistic effect of compounds on target proteins aiding in enhanced insulin activity and could serve as a potential anti-diabetic agent.

Neoastilbin ameliorates sepsis-induced liver and kidney injury by blocking the TLR4/NF-κB pathway.

Sepsis frequently causes systemic inflammatory response syndrome and multiple organ failure in patients. Neoastilbin (NAS) is a flavonoid that plays vital functions in inflammation. This work aims to investigate the protective effects of NAS against sepsis-induced liver and kidney injury and elucidate its underlying mechanisms. The mouse model was established using cecal ligation puncture (CLP) induction. NAS was given to mice by gavage for 7 consecutive days before surgery. Liver and kidney function, oxidative stress, and inflammatory factors in serum or tissues were examined by ELISA or related kits. The expression of relevant proteins was assessed by Western blot. Hematoxylin and eosin and/or periodic acid-Schiff staining revealed that NAS ameliorated the pathological damage in liver and kidney tissues of CLP-induced mice. NAS improved liver and kidney functions, as evidenced by elevated levels of blood urea nitrogen, Creatinine, ALT, and AST in the serum of septic mice. TUNEL assay and the expression of Bcl-2 and Bax showed that NAS dramatically reduced apoptosis in liver and renal tissues. NAS treatment lowered the levels of myeloperoxidase and malondialdehyde, while elevated the superoxide dismutase content in liver and kidney tissues of CLP-induced mice. The levels of inflammatory cytokines (IL-6, TNF-α, and IL-1β) in the serum and both tissues of CLP-injured mice were markedly decreased by NAS. Mechanically, NAS downregulated TLR4 expression and inhibited NF-κB activation, and overexpression of TLR4 reversed the protective effects of NAS against liver and kidney injury. Collectively, NAS attenuated CLP-induced apoptosis, oxidative stress, inflammation, and dysfunction in the liver and kidney by restraining the TLR4/NF-κB pathway.

LRRK2; Communicative Role in the Treatment of Parkinson's Disease and Ulcerative Colitis Overlapping.

Involvement of gastrointestinal inflammation in Parkinson's disease (PD) pathogenesis and movement have progressively emerged. Inflammation is involved in the etiology of both PD and inflammatory bowel disease (IBD). Transformations in leucine-rich recurrent kinase 2 (LRRK2) are among the best hereditary supporters of IBD and PD. Elevated levels of LRRK2 have been reported in stimulated colonic tissue from IBD patients and peripheral invulnerable cells from irregular PD patients; thus, it is thought that LRRK2 directs inflammatory cycles. Since its revelation, LRRK2 has been seriously linked in neurons, albeit various lines of proof affirmed that LRRK2 is profoundly communicated in invulnerable cells. Subsequently, LRRK2 might sit at a junction by which stomach inflammation and higher LRRK2 levels in IBD might be a biomarker of expanded risk for inconsistent PD or potentially may address a manageable helpful objective in incendiary sicknesses that increment the risk of PD. Here, we discuss how PD and IBD share covering aggregates, especially regarding LRRK2 and present inhibitors, which could be a helpful objective in ongoing treatments. English data were obtained from Google Scholar, PubMed, Scopus, and Cochrane library studies published between 1990-December 2022. Inhibitors of the LRRK2 pathway can be considered as the novel treatment approaches for IBD and PD treatment. Common mediators and pathways are involved in the pathophysiology of IBD and PD, which are majorly correlated with inflammatory situations. Such diseases could be used for further clinical investigations.

Asymmetric Dimethylarginine (ADMA) in Cardiovascular Disease, Cardiac Ischemia/reperfusion Injury, and Ischemic Non-obstructive Coronary Artery Disease: Biochemical and Pharmacological Implications

: Several studies have shown that high plasma concentrations of asymmetric dimethylarginine (ADMA), a known endogenous competitive inhibitor of endothelial nitric oxide synthase (eNOS), correlate with the severity of coronary artery disease (CAD), with worsening of cardiac ischemia/reperfusion (I/R) injury and coronary atherosclerosis. It is believed that it may be an important risk factor for myocardial infarction. ADMA, when in high concentrations, can determine a significant decrease in the synthesis and bioavailability of NO (Nitric oxide) and therefore alter the mechanisms of regulation of coronary vasodilation and vasomotor function of epicardial coronary arteries. Higher serum ADMA concentration is associated with worsening of post-ischemic remodeling since coronary angiogenesis, vasculogenesis, and collateral coronary growth are seriously impaired. In addition, there are reasons to believe that elevated plasma ADMA levels are related to the development of diseases affecting coronary microcirculation, such as ischemic non-obstructive coronary artery disease (INOCA). With the aim of providing the pharmacologist engaged in the design and discovery of new ADMA-lowering drugs with a complete examination of the subject, in this review, we discuss the most important studies related to the correlations between serum ADMA levels and cardiovascular diseases mentioned above. In addition, we critically discuss the main aspects of enzymology, synthesis, and metabolism of ADMA as a prerequisite for understanding the molecular mechanisms through which high concentrations of ADMA could contribute to promoting cardiovascular diseases. ADMA represents a new target for pharmacological modulation of cardiovascular endothelial function and therefore, there is a possibility of using selective pharmacological ADMA lowering drugs in cardiovascular disease with endothelial dysfunction and high plasma ADMA levels.

Melatonin Alleviates High Glucose-induced Oxidative Stress and Mitochondrial Dysfunction in Chondrocytes

Background: Hyperglycemia triggers mitochondrial dysfunction in chondrocytes, potentially contributing to cell damage and the onset of osteoarthritis. Objective: This study is undertaken with the objective of examining the protective properties of melatonin against toxicity induced by high glucose in C28I2 human chondrocytes. Methods: To determine non-cytotoxic concentrations of melatonin, various concentrations (10, 25, 50, 75, 100, 500, and 1000 μM) were assessed over different time periods (24, 48, and 72 hours) for their impact on C28I2 cell viability. Following this, cells underwent a pretreatment with melatonin (10 and 100 μM) for 6 hours. This was followed by subjecting the cells to a high concentration of glucose (75 mM) for 48 hours. Oxidative stress markers, including reactive oxygen species (ROS) and malondialdehyde (MDA), alongside the enzymatic activities of glutathione peroxidase, superoxide dismutase, and catalase were quantitatively assessed. To assess mitochondrial function, we evaluated the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio and measured the mitochondrial membrane potential (MMP). Results: Elevated glucose levels significantly increased ROS and MDA levels, accompanied by reduced MMP, an elevated ADP/ATP ratio, and altered antioxidant enzyme activity. Pretreatment with melatonin effectively reversed the mitochondrial toxicity induced by high glucose (75 mM). Conclusion: These results indicate that melatonin exhibits a protective influence against hyperglycemia- induced toxicity in chondrocyte mitochondria.

Curbing Key Digestive Enzymes by Three Plant Extracts for Sustainable Management of Postprandial Hyperglycemia

Background: Diabetes mellitus is a chronic metabolic condition marked by persistently elevated blood sugar levels. Key digestive enzymes viz. α-amylase and α-glucosidase, hydrolyze consumed carbohydrates into glucose which raises the postprandial blood glucose level in a diabetic patient. So, the development of α-amylase and α-glucosidase inhibitors procured from medicinal plants to retard starch digestion is an alternative approach for controlling type 2 diabetes mellitus. Objective: The current study aimed to evaluate the inhibitory potentials of the key digestive enzymes viz. α-amylase and α-glucosidase by the extracts of three medicinal plants; red dragon fruit (Hylocereus polyrhizus) pulp and peel, bamboo (Bambusa vulgaris) shoot, turnip (Brassica rapa L.) shoot and leaf by performing α-amylase and α-glucosidase inhibition assays in vitro. Methods: Inhibition of α-amylase activity was conducted using 3,5-dinitrosalicylic acid method, and 4- Nitrophenyl-α-D-glucopyranoside was used as a substrate to perform α-glucosidase inhibition assay in vitro. Results: Among all the selected sample extracts, red dragon fruit pulp expressed the highest percentage of α-amylase inhibition (59.73 ± 4.33%) at the concentration of 1000 μg/mL which is comparable to standard antidiabetic drug Acarbose (70.59 ± 2.64%), whereas the lowest inhibition was observed in turnip shoot extract (42.48 ± 2.10%) at the same concentration. In terms of α-glucosidase inhibition activity, again, red dragon fruit pulp extract demonstrated the maximum inhibition rate (56.42 ± 2.38%) at 1000 μg/mL concentration. This is respectable in comparison to the reference Acarbose (66.45 ± 1.78%). In contrast, turnip shoot extracts displayed the lowest α-glucosidase inhibition activity (38.27 ± 2.21%) at the same concentration. Conclusion: The current study demonstrated that the red dragon fruit pulp extract possesses substantial antihyperglycemic activity (α-amylase inhibition: 59.73 ± 4.33%, α-glucosidase inhibition: 56.42 ± 2.38%) in vitro, which could be a putative nutraceutical to manage postprandial hyperglycemia.

Expression of Transcriptional Factors of T Helper Differentiation (T-bet, GATA-3, RORγt, and FOXP3), MIF Receptors (CD44, CD74, CXCR2, 4, 7), and Th1, Th2, and Th17 Cytokines in PBMC from Control Subjects and Rheumatoid Arthritis Patients.

The macrophage migration inhibitory factor (MIF) plays a pivotal role in the development of rheumatoid arthritis (RA). Previous research indicates that MIF can trigger the expression of cytokine profiles associated with Th1, Th2, and Th17 responses in peripheral blood mononuclear cells (PBMC) from both RA patients and control subjects (CS). Despite these, few studies to date precisely elucidate the molecular mechanisms involved. The present study aimed to associate the expression of Th differentiation TF (T-bet, GATA-3, RORγt) with MIF receptors (CD44, CD74, CXCR2, 4, 7) and Th1, Th2, and Th17 cytokines in PBMC from CS and RA patients. PBMC from both groups was cultured for 24 h. The expression of the canonical and non-canonical MIF receptors and the TF was determined by flow cytometry. Additionally, multiplex bead analysis was employed to assess the levels of cytokines in the culture supernatants. The findings revealed that T CD4+ lymphocytes in the CS group exhibited a heightened expression of CD74 (p<0.05), whereas RA patients displayed an elevated expression of CXCR7 (p<0.001). Furthermore, T CD4+ lymphocytes from RA patients exhibited greater expression of GATA3, RORγt, and FOXP3, along with elevated levels of pro-inflammatory cytokines compared to the CS group (p<0.001). These results indicate that CD74 is more prominently expressed in PBMC from the CS group, whereas CXCR7 is more expressed in PBMC from RA patients. We also noted an increased secretion of Th17 profile cytokines in RA, potentially influenced by the activation of FOXP3 via CD74 and RORγt through CXCR7 using the endocytic pathway.

Discovery of MAO-A Inhibitors as Antidepressant Based on Virtual Screening

Aim: Major depression and anxiety have increased significantly worldwide since the 2019 outbreak of COVID-19. The development of highly effective antidepressants with low side effects is attracting researchers. Methods: Monoamine oxidase A (MAO-A) is a key enzyme that catalyzes the metabolism of norepinephrine (NE), dopamine (DA), and serotonin (5-HT), etc. Elevated level of MAO-A would lead to increased metabolism of its substrates, thereby causing a decrease in the levels of these neurotransmitter monoamines in the brain leading to depression. Consequently, inhibition of MAO-A was thought to be an effective strategy, as this would treat the root cause of depression. Results and Discussion: Based on the crystal structure of MAO-A, 4 star-hits, as potential MAO-A inhibitors was screened from the compound libraries with central nervous system (CNS) activity by using various computational techniques. Molecular dynamics simulation was used to verify the stability of the ligand- receptor complexes. Conclusion: Furthermore, the ADMET (absorption, distribution, metabolism, excretion and toxicity properties) of the virtual hits were predicted in order to evaluate their lead-like properties and safety. This work provides ideas for the drugs discovery of antidepressant.

Cardiac Evaluation of Children Presenting with Trauma

Background: Trauma is a critical public health issue, particularly impacting the young and caus-ing significant financial and moral losses. Approximately one-third of trauma-related hospitaliza-tions and 20-25% of trauma-related deaths are caused by serious chest injuries. We aimed to determine the prognostic value of changing pediatric global troponin levels in the emergency department after trauma. Materials and Methods: Patients who applied to the emergency department with complaints of trauma between January 1, 2015 and January 31, 2022 were evaluated. Records of pediatric patients between the ages of 0 and 18 were reviewed. The cause and severity of the trauma, electrocardiography and echocardiography results, and laboratory data (biochemical, hemogram, C-reactive protein, pro-BNP, CK-MB, troponin, etc.) of the patients were evaluated. This study is an observational and retrospective. Results: Falling from height was the most prevalent cause of injury, accounting for 43% of cases. Chest trauma was observed in 55 patients (56%). All patients with chest trauma exhibited ele-vated troponin levels. Troponin levels were found to be significantly higher in patients with chest trauma (p=0.011). Conclusions: Our findings highlighted the prognostic importance of cardiac troponins, especially in pediatric patients presenting with trauma.

Management of Patients With a Negative Multiparametric Prostate MRI Examination: AJR Expert Panel Narrative Review.

Multiparametric MRI (mpMRI) of the prostate aids risk stratification of patients with elevated PSA levels. Although most clinically significant prostate cancers are detected by mpMRI, insignificant cancers are less evident. Thus, multiple international prostate cancer guidelines now endorse routine use of prostate MRI as a secondary screening test before prostate biopsy. Nonetheless, management of patients with negative mpMRI results (defined as PI-RADS category 1 or 2) remains unclear. This AJR Expert Panel Narrative Review summarizes the available literature on patients with an elevated screening PSA level and a negative prostate mpMRI result and provides guidance for these patients' management. Systematic biopsy should not be routinely performed after a negative mpMRI examination in patients at average risk but should be considered in patients at high risk. In patients who undergo PSA screening rather than systematic biopsy after negative mpMRI, clear triggers should be established for when to perform a repeat MRI examination. Patients with a negative MRI result followed by negative biopsy should follow their health care practitioners' preferred guidelines concerning subsequent PSA screening for the patient's risk level. Insufficient high-level data exist to support routine use of adjunctive serum or urine biomarkers, artificial intelligence, or PSMA PET to determine the need for prostate biopsy after a negative mpMRI examination.

Hyper IgE Syndromes.

The Hyper IgE Syndromes are rare primary immunodeficiencies characterized by eczema, recurrent skin and respiratory infections and elevated serum IgE levels. Nowadays a geneticmolecular characterization is possible and allows the distinction in various monogenic pathologies, which share some clinical characteristics but also important differences. In addition to long-known STAT3 and DOCK8 gene mutations, in fact, also ZNF341, CARD11, ERBB2IP, IL6R and IL6ST genes mutations can cause the disease. The main clinical manifestations are represented by newborn rash, eczema similar to atopic dermatitis, bacterial and viral skin infections, cold abscesses, respiratory infections with possible pulmonary complications, allergies, gastrointestinal manifestations, malignancies and connective tissue abnormalities. Diagnosis is still a challenge because, especially in the early stages of life, it is difficult to distinguish from other pathologies characterized by eczema and high IgE, such as atopic dermatitis. Several scores and diagnostic pathways have been developed, but it is essential to seek a genetic diagnosis. Treatment is based on prevention and early treatment of infections, meticulous skincare, intravenous immunoglobulins and HSCT, which, in some HIES subtypes, can modify the prognosis. Prognosis is related to the affected gene, but also to early diagnosis, timely treatment of infections and early HSCT.

Linking Gba1 E326K mutation to microglia activation and mild age-dependent dopaminergic Neurodegeneration.

Mutations in the GBA1 gene have been identified as a prevalent genetic risk factor for Parkinson's disease (PD). GBA1 mutations impair enzymatic activity, leading to lysosomal dysfunction and elevated levels of α-synuclein (α-syn). While most research has primarily focused on GBA1's role in promoting synucleinopathy, emerging evidence suggests that neuroinflammation may be a key pathogenic alteration caused by GBA1 deficiency. To examine the molecular mechanism underlying GBA1 deficiency-mediated neuroinflammation, we generated Gba1 E326K knock-in (KI) mice using the CRISPR/Cas9 technology, which is linked to an increased risk of PD and dementia with Lewy bodies (DLB). In the ventral midbrain and hippocampus of 24-month-old Gba1 E326K KI mice, we found a moderate decline in GBA1 enzymatic activity, a buildup of glucosylceramide, and an increase in microglia density. Furthermore, we observed increased levels of pro-inflammatory cytokines and formation of reactive astrocytes in primary microglia and astrocytes, respectively, cultured from Gba1 E326K KI mice following treatment with pathologic α-syn preformed fibrils (PFF). Additionally, the gut inoculation of α-syn PFF in Gba1 E326K KI mice significantly enhanced the accumulation of Lewy bodies in the dentate gyrus of the hippocampus, accompanied by aggravated neuroinflammation and exacerbated non-motor symptoms. This research significantly enhances our understanding of the Gba1 E326K mutation's involvement in neuroinflammation and the cell-to-cell transmission of pathogenic α-syn in the brain, thereby opening new therapeutic avenues.

A Review of Medicinal Plants and Phytochemicals for the Management of Gout.

Gout, characterized by elevated uric acid levels, is a common inflammatory joint disease associated with pain, joint swelling, and bone erosion. Existing treatments for gout often result in undesirable side effects, highlighting the need for new, safe, and cost-effective anti-gout drugs. Natural products, including medicinal plants and phytochemicals, have gained attention as potential sources of anti-gout compounds. In this review, we examined articles from 2000 to 2020 using PubMed and Google Scholar, focusing on the effectiveness of medicinal plants and phyto-chemicals in managing gout. Our findings identified 14 plants and nine phytochemicals with anti-gout properties. Notably, Teucrium polium, Prunus avium, Smilax riparia, Rhus coriaria, Foenic-ulum vulgare, Allium cepa, Camellia japonica, and Helianthus annuus exhibited the highest xa-thine oxidase inhibitory activity, attributed to their unique natural bioactive compounds such as phenolics, tannins, coumarins, terpenoids, and alkaloids. Herbal plants and their phytochemicals have demonstrated promising effects in reducing serum urate and inhibiting xanthine. This review aims to report recent studies on plants/phytochemicals derived from herbs beneficial in gout and their different mechanisms.

DPP2/7 is a Potential Predictor of Prognosis and Target in Immunotherapy in Colorectal Cancer: An Integrative Multi-omics Analysis.

Colorectal cancer (CRC) ranks among the leading causes of cancerrelated deaths. This study aimed to illuminate the relationship between DPP7 (also known as DPP2) and CRC through a combination of bioinformatics and experimental methodologies. A multi-dimensional bioinformatic analysis on DPP7 was executed, covering its expression, survival implications, clinical associations, functional roles, immune interactions, and drug sensitivities. Experimental validations involved siRNA-mediated DPP7 knockdown and various cellular assays. Data from the Cancer Genome Atlas (TCGA) identified high DPP7 expression in solid CRC tumors, with elevated levels adversely affecting patient prognosis. A shift from the N0 to the N2 stage in CRC was associated with increased DPP7 expression. Functional insights indicated the involvement of DPP7 in cancer progression, particularly in extracellular matrix disassembly. Immunological analyses showed its association with immunosuppressive entities, and in vitro experiments in CRC cell lines underscored its oncogenic attributes. DPP7 could serve as a CRC prognosis marker, functioning as an oncogene and representing a potential immunotherapeutic target.

Breathomics Detect the Cardiovascular Disease: Delusion or Dilution of the Metabolomic Signature.

Volatile organic compounds (VOCs) can be subdivided into exogenous and endogenous categories based on their origin. Analyzing the endogenous VOCs can provide insights into maintaining the internal organs' homeostasis. Despite the ongoing development and the current understanding, studies have suggested a link between cardiovascular metabolic alterations in patients with ischemic heart disease and elevated levels of ethane and isoprene detectable through exhaled breath analysis. Conversely, patients with chronic heart failure exhibit elevated acetone and pentane in their exhaled air. These substances originate from disturbances in the heart tissue, including cellular and subcellular modulations. Hypothetically, ethane levels in the exhaled breath analysis can demonstrate the severity of ischemic heart disease and, consequently, the risk of death in the next 10 years due to cardiovascular disease (CVD). Real-time direct mass spectrometry is the preferred method for assessing VOCs in exhaled breath analysis. The accuracy of this analysis depends on several factors, including the selection of the relevant breath fraction, the type of breath collection container (if used), and the pre-concentration technique.

Relationships of Fat Mass Index and Fat-Free Mass Index with Low-Density Lipoprotein Cholesterol Levels in the Tohoku Medical Megabank Community-Based Cohort Study.

Although fat mass (FM) and fat-free mass (FFM) have an impact on lipid metabolism, the relationship between different body composition phenotypes and lipid profiles is still unclear. By dividing the FM and FFM by the square of the height, respectively, the fat mass index (FMI) and fat-free mass index (FFMI) can be used to determine the variations in body composition. This study aimed to investigate the relationship of combined FMI and FFMI with low-density lipoprotein cholesterol (LDL-C) levels. This cross-sectional study comprised 5,116 men and 13,630 women without cardiovascular disease and without treatment for hypertension, and diabetes. Following sex-specific quartile classification, FMI and FFMI were combined into 16 groups. Elevated LDL-C levels were defined as LDL-C ≥ 140 mg/dL and/or dyslipidemia treatment. Multivariable logistic regression models were used to examine the relationships between combined FMI and FFMI and elevated LDL-C levels. Overall, elevated LDL-C levels were found in 1,538 (30.1%) men and 5,434 (39.9%) women. In all FFMI subgroups, a higher FMI was associated with elevated LDL-C levels. Conversely, FFMI was inversely associated with elevated LDL-C levels in most FMI subgroups. Furthermore, the groups with the highest FMI and lowest FFMI had higher odds ratios for elevated LDL-C levels than those with the lowest FMI and highest FFMI. Regardless of FFMI, FMI was positively associated with elevated LDL-C levels. Conversely, in the majority of FMI subgroups, FFMI was inversely associated with elevated LDL-C levels.

Review on Diabetes Mellitus: An Insight into the Current Scenarios, the Challenges of Therapy, and Application of Traditional Drugs

Abstract: Diabetes mellitus, an epidemic of the 21st century, is listed as one of the top ten causes of death around the world by the World Health Organization and is a complicated disease to deal with. Medically, a metabolic disorder characterized by elevated blood glucose levels and altered metabolism of biological macromolecules, mainly carbohydrates. Diabetes mellitus has a worldwide prevalence, and populations of all high, middle, as well as low-income countries, are affected by it. More than 400 million persons are currently living with diabetes. Many risk factors, such as lack of exercise, irregular diet, drinking, and smoking habits, as well as genetic factors, also contribute to the increased incidence of diabetes mellitus in the modern era. The conventional therapies for diabetes are based on insulin, insulin analogues, peptides, and oral hypoglycemics. The primary objective is to lower the elevated blood glucose levels and manage the distress to enhance the quality of life of the patient. The management of diabetes is very crucial to avoid complications having serious consequences such as the extra economic burden due to these complications. Conventional drug therapy has its own adverse effects, and its timely availability and cost are still an issue in many low and middle-income countries. Diabetes mellitus has been reported in various ancient kinds of literature along with various natural remedies (plants/herbals) useful in it. These plant-based remedies offer the benefits of lesser or no adverse effects, easy availability due to natural abundance, and low cost. Therefore, extensive research work is carried out in the past few decades to identify and understand the underlying principles of plant-based/herbal medicines to develop new potential lead molecules and a relatively safer, easily available and more economical alternative treatment therapy for diabetes mellitus.

Skeletal muscle myosin heavy chain expression and 3D capillary network changes in streptozotocin-induced diabetic female mice.

It is not well-understood how type 1 diabetes (T1DM) affects skeletal muscle histological phenotype, particularly capillarisation. This study aimed to analyze skeletal muscle myosin heavy chain (MyHC) fibre type changes and 3D capillary network characteristics in experimental T1DM mice. Female C57BL/6J-OlaHsd mice were categorized into streptozotocin (STZ)-induced diabetic (n = 12) and age-matched non-diabetic controls (n =12). The muscle fibre phenotype of the soleus, gluteus maximus, and gastrocnemius muscles were characterized based on the expression of MyHC isoforms, while capillaries of the gluteus maximus were assessed with immunofluorescence staining, confocal laser microscopy and 3D image analysis. STZ-induced diabetic mice exhibited elevated glucose levels, reduced body weight, and prolonged thermal latency, verifying the T1DM phenotype. In both T1DM and non-diabetic mice, the gluteus maximus and gastrocnemius muscles predominantly expressed fast-twitch type 2b fibers, with no significant differences noted. However, the soleus muscle in non-diabetic mice had a greater proportion of type 2a fibers and comparable type 1 fiber densities (26.2 ± 14.6% vs 21.9 ± 13.5%) relative to diabetic mice. T1DM mice showed reduced fiber diameters (P = 0.026), and the 3D capillary network analysis indicated a higher capillary length per muscle volume in the gluteus maximus of diabetic mice compared to controls (P < 0.05). Overall, T1DM induced significant changes in the skeletal muscle, including shifts in MyHC fibre types, decreased fibre diameters, and increased relative capillarisation, possibly due to muscle fibre atrophy. Our findings emphasize the superior detail provided by the 3D analytical method for characterizing skeletal muscle capillary architecture, highlighting caution in interpreting 2D data for capillary changes in T1DM.

Cuproptosis-related gene LIPT1 as a prognostic indicator in non-small cell lung cancer: Functional involvement and regulation of ATOX1 expression.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths, necessitating a deeper understanding of novel cell death pathways like cuproptosis. This study explored the relevance of cuproptosis-related genes in NSCLC and their potential prognostic significance. We analyzed the expression of 16 cuproptosis-related genes in 1017 NSCLC tumors and 578 Genotype-Tissue Expression (GTEx) normal samples from The Cancer Genome Atlas (TCGA) to identify significant genes. A risk model and prognostic nomogram were employed to identify the pivotal prognostic gene. Further in vitro experiments were conducted to investigate the functions of the identified genes in NSCLC cell lines. LIPT1, a gene for lipoate-protein ligase 1 enzyme, emerged as the central prognostic gene with decreased expression in NSCLC. Importantly, elevated LIPT1 levels were associated with a favorable prognosis for NSCLC patients. Overexpression of LIPT1 inhibited cell growth and enhanced apoptosis in NSCLC. We confirmed that LIPT1 downregulates the copper chaperone gene antioxidant 1 (ATOX1), thereby impeding NSCLC progression. Our study identified LIPT1 as a valuable prognostic biomarker in NSCLC as it elucidates its tumor-inhibitory role through the modulation of ATOX1. These findings offered insights into the potential therapeutic targeting of LIPT1 in NSCLC, contributing to a deeper understanding of this deadly disease.