Medicine in Omics最新文献

Background

Euphorbia thymifolia L. and Euphorbia hirta L. are two medicinally important species used in Ayurveda and are known as Laghudugdhika and Dugdhika respectively. This study was carried out to evaluate the comparative metabolite profiling and anti-cancer activity of E. thymifolia and E. hirta. Chemical profiling was done by High Performance Thin Layer Chromatography (HPTLC) and quantitative estimations of a major class of phytochemicals were done using specified spectrophotometric methods. Detailed metabolite profiling was done by tandem mass spectroscopic evaluation by Q-TOF-LC-MS/MS analysis. Anticancer activity was evaluated using Ehrlich Ascites Carcinoma (EAC) model in mice with 5-fluorouracil as standard.

Results

HPTLC profile showed that most of the chemical contents are similar in both species. Major group of secondary metabolites such as phenolics, flavonoids and sterols were found to be in equal concentration in both species. LC/MS analysis and data processing based on the molecular ion fragmentation pattern led to the identification of 44 compounds from the selected species. Pharmacological evaluation showed that both species possess anti-cancer activity against ascites carcinoma in mice model, however, E. hirta showed a significant dose dependent anticancer activity against EAC induced periotoneal ascites in mice.

Conclusion

The study concluded that the selectd species comparised of variety of active phytoconstrtiuents with anti-cancer properties.

Drug-resistant tuberculosis (DR-TB) epidemics pose a potential threat to global health and are defined by higher morbidity and mortality, sequelae, cost, and complexities. Previously, it has been evidenced that establishing a new drug regimen containing 2–3 new effective drugs may take around 30 years and will be cost-effective. Due to these limitations, drug repurposing has become critical, and the repurposing of existing drugs, licensed for other diseases is the broad alternative for DR-TB treatment. Thus, immunomodulatory drugs are an alternative approach to combat the deadly infectious disease, caused by Mycobacterium tuberculosis. These repurposed drugs target many pathways, and also reduce the risk of acquiring resistance. In this review, we discussed some of the immunomodulatory drugs, and their effectiveness to combat TB.

Echis ocellatus is one of the many viper species that accounts for severe pathophysiological alterations in tissues of organs after envenoming. However, limited information regarding the potential cardiac toxicity due to viper envenoming is available. This current study investigated cardiotoxicity associated with E. ocellatus envenoming in rat model. Twenty (20) male Wistar rats weighing between 140 and 180 g were divided randomly into two groups (n = 10). Rats in group 1 (control) were injected with saline while rats in group 2 were envenomed intraperitoneally with 0.055 mg/kg⁻¹ (LD_6.25) of E. ocellatus venom. The rats were envenomed on day 1 with a repeated dose administered on day 15, afterwards the animals were monitored till day 30. The venom caused significant (P < 0.05) reduction in body and heart weights including the heart index of envenomed rats compared to the control. Levels of malondialdehyde significantly (P < 0.05) increased with decrease in glutathione concentration and catalase activity in heart tissues of envenomed rats. E. ocellatus venom elevated pro-inflammatory cytokines response as levels of tumor necrosis factor-alpha and interleukin1-beta significantly (P < 0.05) increased in cardiac tissues of the envenomed rats compared to control. The venom induced severe morphological defects in the heart tissues of envenomed rats indicating that E. ocellatus venom could actuate cardiotoxicity post envenoming.

When genetic engineering was first developed in the 1970s, it opened new possibilities for genome editing. The life sciences have reaped numerous gains from gene-editing technology. The CRISPR/Cas9 system makes adding or removing sequence-specific amounts of DNA from the genome with ease achievable. CRISPR/Cas9 targeting efficiency improves, and concerted efforts reduce off-target effects. Cancer biology and oncology utilise CRISPR/Cas9 applications to do robust site-specific gene editing, making the technology valuable for research and therapeutic use. CRISPR/Cas9 is quickly evolving into several variations and uses. Helped by CRISPR-based techniques, scientists have developed a simple and inexpensive tool for developing powerful cancer therapies. CRISPR-based gene-editing technologies in oncology, gene editing for personalised medicine and overcoming resistance to cancer therapies, targeted therapies, optimisation of gene-editing technology and future cancer therapeutics are discussed in this review.

This pilot study delineates a protocol to select a set of salivary proteins to distinguish objectively among individual donors. A small subset of proteins (<10%) of > 900 identified by mass spectrometry from wet saliva samples allowed to discriminate among donors supporting the notion that most of the salivary proteome is highly conserved across subjects. Most of these discriminating proteins were involved with immunity, tissue metabolism and regeneration. They were already identified in other saliva proteome studies including those performed with dry saliva samples indicating the likelihood of using wet or dry saliva biospecimens. The differences in the proteomes across subjects may reflect a combination of different lifestyle habits, environmental factors, underlying diseases/conditions, and the many other factors that influence the salivary proteome, but not necessarily age. Application of such proteomic analysis has the potential to increase substantially the value of saliva as a source of proteins in forensic evidence. Additionally, these profiles could possibly be used to develop therapies that are personalized to a patient, built off their individual and unique protein compositions.

Diabetes mellitus (DM) is a metabolic syndrome and is mainly characterized by chronic hyperglycemia. In DM, developing diabetic nephropathy is a major complication. Several studies have shown that Aloe vera (AV) exerts beneficial effects on DM. Proteomic analysis has long been used to systematically study the group of proteins that are being expressed in a given situation. Therefore, in this study, we aimed to evaluate the effect of butanolic fraction of AV (ABF) on the kidneys of type 1 DM rats through proteomic analysis in order to elucidate the protective mechanism of AV. The streptozotocin-induced diabetic model in male Wistar rats was used. We verified that the hypoglycemic effect of ABF lasted up to 6 h after administration. Through proteomic analysis, 36 proteins related to DM were identified with statistical differences between control and diabetics without treatment groups. Thereafter, to verify the results of ABF and insulin, a new statistical analysis was performed considering the treated groups. ABF treatment exerted a beneficial effect by altering the expression of nine of these proteins, among which six of them showed interaction with each other as presented in the string map (10-kDa heat shock, cytochrome P450 2C23, L-lactate dehydrogenase B chain, fructose-bisphosphate aldolase A, transaldolase and cAMP-dependent protein kinase catalytic subunit beta). In conclusion, AV modulated proteins related to mitochondrial function, vascular system and glycolysis/pentose pathway in diabetes situation and these results provide further insights and understanding of the possible molecular mechanisms by which AV may lead to the establishment of treatment and prevention methods for DM-associated kidney damage.

Intra-tumor heterogeneity, the major cause of therapeutic resistance, results from the genetic, epigenetic and microenvironmental selective pressures during tumor progression. However, our knowledge of how this diversity emerges over time remains limited. Single-cell omics approaches, which provide high-resolution data on cellular composition, evolutionary dynamics and clonal relationships in tumor progression, have greatly expanded our toolkit for delineating tumor evolution. Here we summarize recent progress in decoding tumor evolution through single-cell omics measurements and discuss the challenges and opportunities in this emerging field.

Background

The ecological diversity in the tumor microenvironment influences cancer progression and clinical outcomes of patients. However, the complexity of cellular and tissue components hamper quantitative dissection of the tumor microenvironment. In this study, we aimed to develop an efficient and robust artificial intelligence (AI)-empowered framework for the identification of prognostic spatial organization features based on histopathological images.

Results

Using two public H&E image cohorts involving 107,180 hand-delineated image patches, we trained and validated a robust and efficient deep convolutional neural network for accurate tissue classification. With the classification result, we calculated whole-slide and infiltrating spatial organization features (SOFs) for different tissue types. Interestingly, the whole-slide SOFs recapitulated the characteristics of the four Consensus Molecular Subtypes (CMSs) of colorectal cancer (CRC). More specifically, we found that lymphocyte, tumor, mucus, and stroma tissues are significantly more abundant in CMS1, 2, 3, and 4, respectively. Using univariate and multivariate analyses, we identified infiltrating lymphocyte ratio (ILR) and infiltrating stroma ratio (ISR) are significantly associated with relapse-free survival. Based on two independent clinical cohorts, we further demonstrated the combinatorial prognostic value of ILR and ISR. Together, our results suggest that a high level of lymphocyte infiltration may surpass the effect of stromal infiltration. However, stromal infiltration will be essential for RFS in patients with low degrees of immune activity.

Conclusions

We developed CRC-SPA for accurate profiling of spatial organization features using histology images, providing a cost-efficient tool for more quantitative analysis of tumor microenvironment and stratification of patients for more optimized clinical management.

Esophageal squamous cell cancer (ESCC) is one of the most common malignant tumors with high mortality in China, whereas the underlying molecular mechanisms of ESCC are largely unknown. In this study, we aimed to identify the abnormally expressed genes which may play crucial roles in ESCC progression. We performed a weighted gene co-expression network analysis with 1494 differentially expressed genes identified in GSE53624 dataset, and found that the turquoise and black modules were highly correlated with tumor grade of ESCC. Gene ontology enrichment analysis showed that the turquoise module was associated with development and differentiation, and the black module was involved in cell cycle related processes. A total of 3 hub genes: PXMP2, TMEM45B and NEK2 were identified in two modules. Gene expression of 3 genes was associated with overall survival of ESCC patients. Receiver operating characteristic curve analysis showed that all of 3 genes could effectively distinguish ESCC from normal samples in GSE53624 dataset as well as in GSE53622 and TCGA datasets. Gene set enrichment analysis showed that PXMP2 and TMEM45B might be linked to lipid metabolism, and NEK2 was probably related to cell cycle and DNA repair. In addition, both PXMP2 and TMEM45B showed significant hypermethylation of the promoter regions in ESCC, whereas the promoter region of NEK2 was hypomethylated. These findings indicate that PXMP2, TMEM45B and NKE2 may contribute to ESCC progression.