Spatially Resolved Single-Cell Omics: Methods, Challenges, and Future Perspectives.

Overlaying omics data onto spatial biological dimensions has been a promising technology to provide high-resolution insights into the interactome and cellular heterogeneity relative to the organization of the molecular microenvironment of tissue samples in normal and disease states. Spatial omics can be categorized into three major modalities: () next-generation sequencing-based assays, () imaging-based spatially resolved transcriptomics approaches including in situ hybridization/in situ sequencing, and () imaging-based spatial proteomics. These modalities allow assessment of transcripts and proteins at a cellular level, generating large and computationally challenging datasets.

MicroRNAs in Breast Cancer: Diagnostic and Therapeutic Potential.

MicroRNAs (miRNAs) are a large family of small, approximately 20-22 nucleotide, noncoding RNAs that regulate the expression of target genes, at the post-transcriptional level. miRNAs are involved in virtually diverse biological processes and play crucial roles in cellular processes, such as cell differentiation, proliferation, and apoptosis. Accumulating lines of evidence have indicated that miRNAs play important roles in the maintenance of biological homeostasis and that aberrant expression levels of miRNAs are associated with the onset of many diseases, including cancer.

Noncoding RNAs in DNA Damage Response: Opportunities for Cancer Therapeutics.

DNA repair machinery preserves genomic integrity, which is frequently challenged through endogenous and exogenous toxic insults, and any sort of repair machinery malfunctioning ultimately manifests in the form of several types of terrible human diseases such as cancers (Hoeijmakers, Nature 411(6835): 366-374, 2001). Noncoding RNAs (ncRNAs) are crucial players of DNA repair machinery in a cell and play a vital role in maintaining genomic stability, which is essential for its survival and normal functioning thus preventing tumorigenesis. To preserve the integrity of the genome, cells initiate a specific cellular response, recognized as DNA damage response (DDR), which includes several distinct DNA repair pathways.

Phosphatidyl inositol-3 kinase (PIK3CA) E545K mutation confers cisplatin resistance and a migratory phenotype in cervical cancer cells.

The phosphatidylinositol-3 kinase (PI3K)/Akt/mTOR signaling pathway is activated in many human cancers. Previously, we reported that patients with early stage cervical cancer whose tumours harbour PIK3CA exon 9 or 20 mutations have worse overall survival in response to treatment with radiation and cisplatin than patients with wild-type PIK3CA. The purpose of this study was to determine whether PIK3CA-E545K mutation renders cervical cancer cells more resistant to cisplatin and/or radiation, and whether PI3K inhibition reverses the phenotype.

Alleviation of doxorubicin-induced nephrotoxicity and hepatotoxicity by chrysin in Wistar rats.

Unlabelled: Abstract Objective: Doxorubicin (DXR) is an anticancer drug used in the treatment of many human malignancies. However, its clinical use is limited because of several side effects like cardiotoxicity, nephrotoxicity and hepatotoxicity. In the present study, we investigated the protective efficacy of chrysin against DXR-induced oxidative stress, nephro- and hepatotoxicity in male Wistar rats using biochemical and histopathological approaches.

GNAS1 (Gαs) gene T393C polymorphism and renal cell carcinoma risk in a North Indian population: a case-control study.

Aim: Heterotrimeric G protein α-subunit Gαs is required for activation of adenylyl cyclase and generation of cyclic adenosine monophosphate (cAMP) in cells and plays a key role in multiple signal transduction pathways, linked to proapoptotic processes in cancer cells. This study investigated whether Gαs gene polymorphism was associated with increased renal cell carcinoma (RCC) risk in the North Indian population. In the present study, genotyping of GNAS1 gene in 196 RCC cases and 250 healthy controls was performed via polymerase chain reaction-restriction fragment length polymorphism.

Risk of renal cell carcinoma and polymorphism in phase I xenobiotic metabolizing CYP1A1 and CYP2D6 enzymes.

The progressive increase in sporadic renal cell carcinoma (RCC) observed in industrialized countries supports the opinion that certain carcinogens present in the environment (tobacco smoke, drugs, pollutants, and dietary constituents) may affect the occurrence and progression of this disease in developing countries like India. The polymorphism of the enzymes involved in metabolism of such environmental factors may, therefore, confer variable propensity to RCC. The possible association between RCC and a polymorphism of the CYP1A1 and CYP2D6 genes specific to the Indian population was examined using peripheral blood DNA from 196 RCC cases and 250 population controls with detailed data of clinicopathologic characteristics for the disease.

Modulatory effects of gentisic acid against genotoxicity and hepatotoxicity induced by cyclophosphamide in Swiss albino mice.

Objectives: This study evaluated the protective effects of gentisic acid (GA) against genotoxicity and hepatotoxicity induced by cyclophosphamide (CP) in Swiss albino mice.

Methods: Mice were pretreated with GA orally at doses of 50 and 100 mg/kg for 14 consecutive days before the administration of a single intraperitoneal dose of 50 mg/kg CP. The ameliorative effect of GA on genotoxicity was studied using the in-vivo bone marrow micronuclei induction test, DNA integrity and alkaline unwinding assay.

Nephroprotective action of Peucedanum grande against cadmium chloride induced renal toxicity in Wistar rats.

Cadmium is a known industrial pollutant which accumulates in the kidney and its exposure leads to the production of reactive oxygen species (ROS). The present study was carried out to evaluate the protective effects of Peucedanum grande against CdCl2 induced renal toxicity in Wistar rats. Wistar rats were subjected to oral pre-treatment of P.

Role of VHL gene mutation in human renal cell carcinoma.

The Von Hippel-Lindau (VHL) is an inherited neoplasia syndrome caused by the inactivation of VHL tumor suppressor gene, and somatic mutation of this gene has been related to the development of sporadic clear cell renal carcinoma. The affected individuals are at higher risk for the development of tumor in other organs, which include pheochromocytomas, retinal angioma, pancreatic cysts, and CNS hemangioblastomas. The VHL mRNA encodes a protein (pVHL) that contains 213 amino acid residues which migrate with an apparent molecular weight of 24 to 30 kDa.

Hesperidin alleviates acetaminophen induced toxicity in Wistar rats by abrogation of oxidative stress, apoptosis and inflammation.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but at high dose it leads to undesirable side effects, such as hepatotoxicity and nephrotoxicity. The present study demonstrates the comparative hepatoprotective and nephroprotective activity of hesperidin (HD), a naturally occurring bioflavonoid against APAP induced toxicity. APAP induces hepatotoxicity and nephrotoxicity as was evident by abnormal deviation in the levels of antioxidant enzymes.

Impact of glutathione transferase M1, T1, and P1 gene polymorphisms in the genetic susceptibility of North Indian population to renal cell carcinoma.

In this study, we investigated the association of GSTP1, GSTM1, and GSTP1 genetic variants with renal cell carcinoma (RCC) among North Indian patients. The difference in frequency of the GSTT1 null genotype between cases and control subjects was statistically significant (active ver. null, odds ratio [OR]=0.

Vitamin D receptor FokI and BsmI gene polymorphism and its association with grade and stage of renal cell carcinoma in North Indian population.

Vitamin D exerts its activity through binding to the high-affinity nuclear vitamin D receptor (VDR), and majority of genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC) etiology in our study population. This study investigated whether VDR gene polymorphisms were associated with increased risk and prognosis of RCC in the North Indian population.

Methylation of the APAF-1 and DAPK-1 promoter region correlates with progression of renal cell carcinoma in North Indian population.

Aberrant promoter hypermethylation of cancer associated genes occur frequently during carcinogenesis and may serve as a cancer biomarker. The aim of this study was to investigate the occurrence and relevance of promoter methylation of the tumor suppressor DAPK-1, APAF-1 () and SPARC in relation to different pathological stages and histological grades of tumor progression that might act as possible independent prognostic factor in the susceptibility towards renal cell carcinoma (RCC) in North Indian population. Three tumor suppressor gene promoters namely APAF-1, DAPK-1 and SPARC were assessed by methylation-specific PCR (MS-PCR) in 196 primarily resected renal cell tumors paired with the corresponding normal tissue samples.

Preclinical renal cancer chemopreventive efficacy of geraniol by modulation of multiple molecular pathways.

In the present study, we have evaluated the chemopreventive potential of geraniol (GOH), an acyclic monoterpene alcohol against ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and carcinogenesis in Wistar rats. Chronic treatment of Fe-NTA induced oxidative stress, inflammation and cellular proliferation in Wistar rats. The chemopreventive efficacy of GOH was studied in terms of xenobiotic metabolizing enzyme activities, LPO, redox status, serum toxicity markers and the expression of putative nephrotoxicity biomarker Kim-1, tumor suppressor gene P53, inflammation, cell proliferation and apoptosis related genes in the kidney tissue.

Glycyrrhizic acid: a phytochemical with a protective role against cisplatin-induced genotoxicity and nephrotoxicity.

Aims: Glycyrrhizic acid (GA) is a main sweetening component of licorice roots and has been found to be associated with multiple therapeutic properties. In this study, we used GA as a protective agent against the clastogenic and nephrotoxic effects of cisplatin (CP).

Main Methods: Mice were given a prophylactic treatment of GA orally at doses of 75 and 150mg/kg body weight for seven consecutive days before the administration of a single intraperitoneal dose of CP at 7mg/kg body weight.

Rutin attenuates cisplatin induced renal inflammation and apoptosis by reducing NFκB, TNF-α and caspase-3 expression in wistar rats.

Cisplatin is an effective chemotherapeutic agent that displays dose-limiting nephrotoxicity. In the present study the wistar rats were subjected to concurrent prophylactic oral treatment of rutin (75 and 150 mg/kgb.wt.