Progress of engineered bacteria for tumour therapy.

Finding novel therapeutic modalities, improving drug delivery efficiency and targeting, and reducing the immune escape of tumor cells are currently hot topics in the field of tumor therapy. Bacterial therapeutics have proven highly effective in preventing tumor spread and recurrence, used alone or in combination with traditional therapies. In recent years, a growing number of researchers have significantly improved the targeting and penetration of bacteria by using genetic engineering technology, which has received widespread attention in the field of tumor therapy. In this paper, we provide an overview and assessment of the advancements made in the field of tumor therapy using genetically engineered bacteria. We cover three major aspects: the development of engineered bacteria, their integration with other therapeutic techniques, and the current state of clinical trials. Lastly, we discuss the limitations and challenges that are currently being faced in the utilization of engineered bacteria for tumor therapy.

COVID-19 and gastroenteric manifestations.

Coronavirus disease 2019 (COVID-19), caused by the infection of a novel coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)], has become a pandemic. The infection has resulted in about one hundred million COVID-19 cases and millions of deaths. Although SARS-CoV-2 mainly spreads through the air and impairs the function of the respiratory system, it also attacks the gastrointestinal epithelial cells through the same receptor, angiotensin converting enzyme 2 receptor, which results in gastroenteric symptoms and potential fecal-oral transmission. Besides the infection of SARS-CoV-2, the treatments of COVID-19 also contribute to the gastroenteric manifestations due to the adverse drug reactions of anti-COVID-19 drugs. In this review, we update the clinical features, basic studies, and clinical practices of COVID-19-associated gastroenteric manifestations.

Pharmacotherapics Advice in Guidelines for COVID-19.

Since December 2019 to May 2020, coronavirus disease 2019 (COVID-19) has infected over 6 million people worldwide. Due to its sudden and rapid outbreak, effective treatment for COVID-19 is scarce. Based on national clinical trials of novel treatments, China, Italy, Germany, and other countries and organizations have published multiple guidelines for COVID-19 and advised many medicines, such as chloroquine and tocilizumab. In this paper, we summarize the pharmacotherapy for COVID-19 according to those guidelines, highlight updates of the pharmacotherapy guidelines, and review the efficacy and safety of the indicated anti-COVID-19 drugs.

MIR4532 gene variant rs60432575 influences the expression of KCNJ11 and the sulfonylureas-stimulated insulin secretion.

PURPOSE: Diabetes mellitus is a major chronic disease and causes over one million deaths. KCNJ11 genetic polymorphisms influence the response of first-line oral antidiabetic agent sulfonylureas. Hsa-miR-4532 correlates with diabetic nephropathy and has a high abundance in urine. MIR4532 rs60452575 G>A variant changes the mature sequence of hsa-miR-4532. We studied whether the genetic polymorphisms of MIR4532 rs60452575 would influence KCNJ11 expression and sulfonylurea-stimulated insulin secretion or not. METHODS: To estimate the influence that rs60452575 G>A variant has on the interaction of hsa-miR-4532 and KCNJ11, we constructed a pmirGLO vector containing 3' UTR of KCNJ11 and co-transfected it with wild-type and mutant hsa-miR-4532 mimics into HEK293 cells; and we overexpressed wild-type and mutant hsa-miR-4532 mimics into HEK293 cells and MIN6 cells to access its effects on KCNJ11 expression and response of sulfonylureas. RESULTS: MIR4532 rs60452575 G>A variant appeared to disrupt the repression of KCNJ11 expression in both cell lines, and reduce the sulfonylurea-stimulated insulin secretion by breaking the binding of the hsa-miR-4532 to 3' UTR of KCNJ11 in MIN6 cells. CONCLUSIONS: Our study indicates that MIR4532 rs60452575 variant influences KCNJ11 expression and sulfonylurea response. It might be a potential predictive factor of sulfonylureas therapy.

Drug-induced hyperglycaemia and diabetes: pharmacogenomics perspectives.

Drug-induced diabetes is widely reported in clinical conditions, and it is becoming a global issue because of its potential to increase the risk of severe cardiovascular complications. However, which drug mechanisms exert their diabetogenic effects and why the effects present significant inter-individual differences remain largely unknown. Pharmacogenomics, which is the study of how genomic variation influences drug responses, provides an explanation for individual differences in drug-induced diabetes. We highlight that pharmacogenomics can be involved in regulating the expression of genes in signaling pathways related to the pharmacokinetics or pharmacodynamics of drugs or the pathogenesis of diabetes, contributing to the differences in drug-induced glucose impairment. The pharmacogenomics studies of the major diabetogenic drugs are reviewed, including calcineurin inhibitors, antipsychotics, hormones, and antihypertensive drugs. We intend to elucidate the genetic basis of drug-induced diabetes and pave the way for the precise use of these drugs in the clinic.