Medicine in Omics最新文献

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and insulin resistance. Sulforaphane (SFN) is a widely distributed isothiocyanate found in cruciferous vegetables. This study investigated the role of SFN on the hypothalamic-pituitary-ovarian axis in PCOS rats. Twenty-four female rats randomized into group A control received 2 ml of normal saline. Group B received 4 mg/kg body weight (bwt) I.P of estradiol valerate (EV) on the first day, groups C received 100 mg/kg bwt of SFN orally, and Group D received I.P 4 mg/kg bwt of EV follow by 100 mg/kg bwt of SFN orally. All administrations were done once daily for 30 days. Final body weight, estrous cycle, ovarian weight, blood glucose, serum sex hormones levels, serum lipid profile, ovarian antioxidants assay, ovarian inflammatory cytokines, and ovary and pituitary histology were assessed.

The PCOS rats exhibited the characteristic features of PCOS. Disturbed ovarian cyclicity, histopathological alterations, decreased the number of healthy follicles and corpora lutea and increased degenerated and cystic follicles were detected by light microscopic studies. A significant increase in final body weight, ovarian weight, blood glucose, sex steroids hormone levels, and antioxidant assays in PCOS rats. Sulforaphane reduces the elevated level of serum sex steroids hormone, lipid profile, ovarian diameter, and cysts and restores healthy follicles in PCOS rats. SFN reduces the upraised levels of ovarian oxidant and inflammatory cytokines and increases the suppressed antioxidant enzymes.

Sulforaphane thus ameliorates the disturbed hormonal levels, lipid profile, and antioxidant status in PCOS rats through its antioxidant and anti-inflammatory capacity.

The physiological function of the liver in the overall disposal of postprandial glucose is important in the management of diabetes. Our recent research showed that benzylidene indanone derivative 2-(3,4-dihydroxybenzylidene)-4-methoxy-2,3-dihydro-1H-inden-1-one (2-BI) showed antihyperglycemic activity, but its role in glucose homeostasis in the liver is unknown. ¹H NMR metabolomics approach was used to unravel the effectiveness of 2-BI, on hepatic glucose production in fructose-streptozotocin (STZ) diabetics. Diabetes was induced in Sprague–Dawley rats using fructose-streptozotocin. Metabolites were extracted from the liver tissue and analyzed by ¹H NMR spectroscopy. Pathway analysis was performed on the identified metabolites. The unsupervised principal components analysis score plot showed clear differentiation. The control group (NC) was clearly separated from the diabetic group (DBC) and was clustered near the treated diabetic groups (DBI and DGT). There is a significant (p < 0.01) increased level of 12 metabolites in diabetes rats that are crucial in liver glucose homeostasis. Treatment with 2-BI was able to lower the level of these metabolites. Detailed pathway analysis of the spiked metabolite levels shows an effect on the glycolysis/gluconeogenesis, butanoate, amino acid, nitrogen, and nucleotide (pyrimidine) metabolism. 2-BI reduced hyperglycemia in diabetic rats via the attenuation of hepatic glucose production and advancement of liver insulin sensitivity.

This study aimed to elucidate the metabolic interplay between food-borne bacteria, gut methanogens, and probiotic bacteria using the host-microbe-drug interactome. This study also aimed to identify suitable drug combinations that could effectively combat food-borne infections without adversely affecting the normal gut microbes. In this study, the system medicine framework comprised 2654 edges and 1609 nodes, with 1370 interacting human genes. Through network modeling analysis, we identified interactions among 39 human target genes for food-borne bacteria, 11 targets for gut methanogens, and nine targets for probiotic bacteria. Gut methanogens target common human genes for their pathophysiological functions. Linoleic acid has emerged as a crosstalk metabolite that determines the abundance of foodborne bacteria. Gut microbes commonly share butyric acid, CO₃, and formaldehyde as metabolic precursors. Most antibiotics interact with human genes that target the gut methanogens and probiotic bacteria. Our study identified fusidic acid, nabiximol, oxacillin, ampicillin, phenoxymethylpenicillin, and cefdinir as repurposable antibiotics against foodborne bacterial infections. Chloroquine, an antimalarial drug, has been suggested as a potential repurposable drug for foodborne infections, owing to its indirect association with many foodborne bacteria via host-mediated interactions. Thus, our system medicine framework could potentially aid in suggesting repurposable antibiotics against food-borne bacterial infections, without affecting beneficial microbes in the human gastrointestinal tract.

The heart is a complex organ that starts to function by the end of the third week of gestation. Cardiovascular diseases attribute to the leading causes of death globally. The explosion of technological advances and computational tools for the analysis of next generation sequencing data has opened new avenues for comprehending the underlying regulatory mechanisms of complex disorders. The transcriptomic and genomic aspects of genes, non-coding RNAs and transcription factors have largely assisted understanding cardiogenesis and cardiovascular disease. The widespread application of transcriptomic methods has assisted in the screening of huge number of differentially expressed non-coding RNAs and their projected role as therapeutic targets and biomarkers. Transcriptomic profiling, including techniques such as RNA sequencing (RNA-Seq) has enabled the comprehensive characterization of gene expression patterns at various stages of embryonic and postnatal heart development. In the context of cardiac diseases, transcriptomic analyses have provided unprecedented insights into the molecular alterations associated with conditions such as myocardial infarction, heart failure, arrhythmias, and congenital heart defects. This review presents an overview of recent advancements in transcriptomic research aimed at unraveling the intricate genetic and molecular networks governing heart development, as well as in cardiac diseases. In this review, we attempted to systematically review the transcriptomic experiments performed to identify significant genes, miRNAs and lncRNAs with biomarkers therapeutic potential, meta-analysis of multiple samples, and ceRNA networks in heart diseases.

Background

Mutations in gastric cancer may remain harmless despite mutations that can turn oncogenic. Although omics technologies have supplied a clear view of mutations and driver genes in cancers, the pathology of gastric cancer still is unknown.

Objective

This study aims to understand mutations of genes that relate to telomere maintenance in gastric cancer.

Methods

We used transcriptomic and proteomic data from normal and gastric cancer patients to decide the relationship between genes and proteins. We ranked the gene-protein pairs with the Spearman correlation and subjected the differently ranked genes for functional analysis. We performed the co-expression analysis to select the genes from functional analysis. Then we assessed the selected genes for mutations and thereafter neoantigen analysis.

Results

We identified 20 genes through differential ranking based on Spearman correlation of gene-protein pairs. Among these, ERCC1, MRE11A, RAD50, TP53BP1, and YWHAE were linked to critical functions like DNA repair, apoptosis, and stress response. Gene prioritization focused on these five genes, and from them through gene co-expression, RAD50, TP53BP1, and YWHAE were selected. Mutational analysis revealed prevalent C > T and G > A mutations. These genes were associated with elderly patients, specific histologic grades, and types of gastric cancer. Importantly, these mutations generated neoantigens with potential for immunotherapeutic targeting.

Conclusion

Our extensive research shows the complex genetic makeup of gastric cancer and its potential effects on diagnosis and treatment. The identified genes and the mutations linked to them offer important information on the molecular processes behind gastric cancer progression. These results set the foundation for additional research and immunotherapeutic applications in the field of gastric cancer.

Turkey is a transcontinental nation with much of its territory in western Asia and southeast Europe, and it is the 6th most affected country by SARS-CoV-2 globally, so far, many mutations have occurred within this short period of time. The present study mainly focused on identifying genotypic variants and proteomic mutations, along with the folding rate and virulence action of Turkey SARS-CoV-2 isolates. The phylogenomic study reveals that the first origination of SARS-CoV-2 isolates (2020) in Turkey has more chance of an occurrence of mutation rate during evolution/new origination. 53 genotypic- and 45 proteomic variants among 83 isolates were found. The genotypic and proteomic variants from 2022 isolates have six times higher mutation rates than 2020 isolates. The highest number of mutations occurred in the 2022 isolate (ERAGEM-OM-1104/2022), with 60 mutations in the G53 variant, followed by 44 mutations in the G49 variant (ERAGEM-DEL-1103/2021) and 42 mutations in the G50 variant (Ank_DLT/2021). Also, we identified 38 novel mutations among 45 proteomic variants. The predicted virulence mechanism of some ORFs such as Nsp1, Nsp3, Nsp4, Nsp5, Nsp8, 2′O-ribose, Spike, Orf3a, Envelope, Orf7b, Orf8, and Nucleocapsid shows high virulence and transmission rate. Hence, our findings would help the researchers to develop new anti-virals against new variants from Turkey’s SARS-CoV-2 isolates.

Antimicrobial peptides are multi-functional peptides that possess a broad range of mechanisms of action. They have been investigated as novel therapeutic options in the field of infectious diseases, but an increasing number of publications suggest that they also play an important role in the pathology of cancer.

Here, using an in silico approach, we investigated the pathways associated with LL-37, the only human member of the cathelicidin family of antimicrobial peptides, in lung squamous cell and in invasive breast carcinomas.

We found that LL-37 is implicated in different and even opposing cell responses, depending on the type of cancer, and participates in intriguing molecular processes, such as platelets activity, coagulation and extracellular matrix organization.

Male infertility is a challenging clinical condition that threatens global reproductive health. Majority of the issues found in testicular dysfunction are associated with oxidative stress. The present study investigated the protective effect of pomegranate fruit extract against Fe²⁺- mediated oxidative testicular injury using ex vivo experimental models. Testicular oxidative injury was induced by incubating testes tissues in Krebs buffer and FeSO₄.7H₂0 solution, and treated by co-incubating with different concentrations (30–240 μg/mL) of pomegranate fruit extract for 90 min (37 °C), with gallic acid serving as the standard antioxidant. Oxidative injury induction led to significant (p < 0.05) elevation of testicular malondialdehyde and LDL-cholesterol concentration, acetylcholinesterase, ATPase, fructose-1,6-bisphosphatase, glycogen phosphorylase and lipase activities. These were concomitantly accompanied by depleted levels of reduced glutathione, glycogen, total cholesterol, triglyceride and HDL-cholesterol and activities of superoxide dismutase, catalase, ENTPDase and 5′Nucleotidase. It also led to distorted testicular histological architecture. Treatment with the fruit extract markedly reversed these levels and activities and preserved testicular morphology. Octadecenoic acid, 1,2,3-propanetriyl ester, (E,E,E)-; squalene and cholesterol, while concomitantly generating 6-Octadecenoic acid, (Z)-; (2Z)-2-Octenoic acid; methyl tetradecanoate; methyl 14-methylpentadecanoate; octadecanoic acid, 2-[(1-oxohexadecyl)oxy]ethyl ester and cholestan-3-ol, 2-methylene-, (3.beta.,5.alpha.)-. This was accompanied by the deactivation of alpha linolenic acid and linoleic acid metabolism, and steroidogenesis. Treatment with pomegranate depleted the oxidative-generated metabolites, while concomitantly generating arachidonic acid, cholesterol margranate and ethyl lithocholate, and reactivating the inactivated pathways. The results indicate the protective effect of pomegranate fruit juice against oxidative testicular injury.

Mycobacterium tuberculosis (Mtb) is a causative agent of the infectious disease tuberculosis (TB), which has hampered susceptible populations in modern-day societies for years. Additionally, the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains has intensified this global health issue. Each year the global death tally spikes by 1.6 million, and additional 10.6 million new cases of TB. Researchers are trying to find a treatment, mainly emphasizing the anti-tubercular drugs and/or vaccines that could potentially control the spread of TB to manage the associated health issue. To date, more than 20 anti-tubercular drugs have been developed and used at various stages of TB. The current review aims to discuss/describe useful information about available TB treatments and anti-tubercular resistance. Moreover, we also highlighted diagnostic approaches and current drug reserves for drug-resistant TB (DR-TB).

Ovarian cancer is a fatal disease requiring great attention from the scientific community to find novel ways for diagnosis and treatment. Most ovarian malignancies, or 90% of cases, are epithelial ovarian cancers. HGSC (High Grade Ovarian Cancer) is the most prevalent subtype, and the majority of women who are diagnosed with it eventually develop resistance to standard treatments. Expression of genes linked to these immune pathways and increased cytotoxic immune cell infiltration is primarily associated with HGSC cancer that shows DNA damage repair gene deficiency and high chromosomal instability. Currently, chemotherapy, radiation, and cytoreduction are the most common forms of treatment; nevertheless, in the absence of targeted therapies, patients experience unfavorable side effects and develop drug resistance. It is critical to understand the intricate biology of the disease and find relevant biomarkers in order to make an early diagnosis or anticipate how a patient will respond to a given treatment. Interferon activating medicines have been studied as a potential means of enhancing anti-tumor immunity in ovarian cancer. Chemical and biological nano-sensors have also been developed to detect different types of cancers, including ovarian cancer. Further, the application of nanotechnology for diagnostic and therapeutic purposes makes it a more convenient, target-specific, and side effect free delivery system for ovarian cancer treatment. A combination of nanotechnology with the physiological biomarkers and therapeutic agents created a novel system of nano theranostics, which have the potential of real-time monitoring and diagnosis and simultaneous delivery of the therapeutic agent for the treatment of ovarian cancer.