The liver-derived exosomes stimulate insulin gene expression in pancreatic beta cells under condition of insulin resistance.

Introduction: An insufficient functional beta cell mass is a core pathological hallmark of type 2 diabetes (T2D). Despite the availability of several effective pharmaceuticals for diabetes management, there is an urgent need for novel medications to protect pancreatic beta cells under diabetic conditions. Integrative organ cross-communication controls the energy balance and glucose homeostasis. The liver and pancreatic islets have dynamic cross-communications where the liver can trigger a compensatory beta cell mass expansion and enhanced hormonal secretion in insulin-resistant conditions. However, the indispensable element(s) that foster beta cell proliferation and insulin secretion have yet to be completely identified. Exosomes are important extracellular vehicles (EVs) released by most cell types that transfer biological signal(s), including metabolic messengers such as miRNA and peptides, between cells and organs. Methods: We investigated whether beta cells can take up liver-derived exosomes and examined their impact on beta cell functional genes and insulin expression. Exosomes isolated from human liver HepG2 cells were characterized using various methods, including Transmission Electron Microscopy (TEM), dynamic light scattering (DLS), and Western blot analysis of exosomal markers. Exosome labeling and cell uptake were assessed using CM-Dil dye. The effect of liver cell-derived exosomes on Min6 beta cells was determined through gene expression analyses of beta cell markers and insulin using qPCR, as well as Akt signaling using Western blotting. Results: Treatment of Min6 beta cells with exosomes isolated from human liver HepG2 cells treated with insulin receptor antagonist S961 significantly increased the expression of beta cell markers Pdx1, NeuroD1, and Ins1 compared to the exosomes isolated from untreated cells. In line with this, the activity of AKT kinase, an integral component of the insulin receptor pathway, is elevated in pancreatic beta cells, as represented by an increase in AKT's downstream substrate, FoxO1 phosphorylation. Discussions: This study suggests that liver-derived exosomes may carry a specific molecular cargo that can affect insulin expression in pancreatic beta cells, ultimately affecting glucose homeostasis.

Differentiation of Pancreatic Beta Cells: Dual Acting of Inflammatory Factors.

In the past decades, scientists have made outstanding efforts to treat diabetes. However, diabetes treatment is still far from satisfactory due to the complex nature of the disease and the challenges encountered in resolving it. Inflammatory factors are key regulators of the immune system's response to pathological insults, organ neogenesis, rejuvenation of novel cells to replace injured cells and overwhelming disease conditions. Currently, the available treatments for type 1 diabetes include daily insulin injection, pancreatic beta cell or tissue transplantation, and gene therapy. Cell therapy, exploiting differentiation, and reprogramming various types of cells to generate pancreatic insulin-producing cells are novel approaches for the treatment of type 1 diabetes. A better understanding of the inflammatory pathways offers valuable and improved therapeutic options to provide more advanced and better treatments for diabetes. In this review, we investigated different types of inflammatory factors that participate in the pathogenesis of type 1 diabetes, their possible dual impacts on the differentiation, reprogramming, and fusion of other stem cell lines into pancreatic insulin-producing beta cells, and the possibility of applying these factors to improve the treatment of this disease.

SARS-CoV-2 and pancreas: a potential pathological interaction?

The widespread extrapulmonary complications of coronavirus disease 2019 (COVID-19) have gained momentum; the pancreas is another major target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we take a closer look into potential pathological interactions. We provide an overview of the current knowledge and understanding of SARS-CoV-2 infection of the pancreas with a special focus on pancreatic islets and propose direct, indirect, and systemic mechanisms for pancreas injury as result of the COVID-19-diabetes fatal bidirectional relationship.

The trend of enteropathogenic Escherichia coli towards atypical multidrug resistant genotypes.

The aim of this study was to investigate the prevalence of multidrug resistance (MDR) in atypical enteropathogenic Escherichia coli (EPEC) genotypes among 547 diarrheal children. All E. coli isolates with eae+stx1-stx2- genotypes included in this study and atypical property of EPEC was characterized by the absence of Bundle-forming pili (bfpA gene). Bacterial pathogens were detected in 70 patients (12.8%) among which atypical EPEC (5.3%) were the most common. The higher resistance rate was seen to tetracycline (70%), cotrimoxazole (60%) and nalidixic acid (53.3%) related to MDR phenotype in 63.3% of isolates. The presence of class 1 and 2 integrons was 30% and 6.6% with the dominance of dfrA, aadA gene cassettes among the isolates. Eleven out of 21 phenotypically tetracycline-resistant isolates (52.38%) harboured one or two tetracycline resistance genes (A-D) which shows the incapability of known data to reasonable tetracycline resistance phenotypes among EPEC isolates. A high level of genotypic diversity was seen among the isolates by Pulsed-field gel electrophoresis method which ranged from 89.7 to 29% and no clear correlation was obtained between tetracycline resistance or integron carriage and specific pulsotypes. In conclusion, the data presented here add to knowledge about the heterogeneous nature of MDR EPEC population in Iran which has a growing tendency towards atypical genotypes. The distribution of integrons among EPEC isolates in Iran is decreasing; although, the resistance gene content is almost stable through years.

Biofilm Formation and Virulence Factors Among Pseudomonas aeruginosa Isolated From Burn Patients.

BACKGROUND: Pseudomonas aeruginosa possesses a variety of virulence factors and infections caused by multidrug-resistant P. aeruginosa (MDRPA) in burn patients are a public health problem. OBJECTIVES: The aim of this study was to determine the antibiotic resistance pattern, the biofilm formation, the prevalence of MDRPA and two virulence genes (nan1 and exoA) among P. aeruginosa isolated from burn patients. PATIENTS AND METHODS: A total of 144 isolates of P. aeruginosa were collected from burn patient at the Burn Centre of Tehran, Iran, between March 2013 and July 2013. Antibiotic susceptibility test was performed via agar disk diffusion method. The ability of producing biofilm was examined by crystal violet microtiter plate assay and the prevalence of the exoA and nan1 genes among the isolates was determined by polymerase chain reaction (PCR). RESULTS: A high rate of resistance was seen against ciprofloxacin (93.7%), aztreonam (86.8%), piperacillin (85.4%), ceftazidime (82.6%), amikacin (82%) and imipenem (79.2%). In total, 93.1% of the isolates were characterized as MDRPA. Biofilm formation was seen in 92.4% of the isolates. The prevalence of the exoA and nan1 genes were 75% and 11.8% among the isolates, respectively. CONCLUSIONS: The high rate of MDRPA and its ability to produce biofilm is an alarm for public health. The statistical analysis showed that biofilm production in the MDRPA isolates was significantly higher than that in the non-MDRPA isolates (P < 0.001).

Clonal Dissemination of a Single Vibrio cholerae O1 Biotype El Tor Strain in Sistan-Baluchestan Province of Iran During 2013.

Although much is known about the mechanisms affecting cholera spread, cholera outbreaks occur annually in Iran. The aim of this study was to characterize and assess the clonal correlation of strains obtained from an outbreak in 2013 in Iran. Thirty-three strains of Vibrio cholerae were isolated from stool sample of patients majority of them belonged to Afghan nationality. PCR and sequencing analysis was performed to characterize virulence and resistance associates genes and cassettes. Clonality of isolates was assessed by Pulsed-field gel electrophoresis (PFGE) method. The ctx, zot, and tcp genes were present in 100 % of isolates. The wbeT gene was absent in all V. cholerae outbreak isolates, integrity of which is essential for Ogawa phenotype. This correlates with Inaba phenotype of all isolates under study. Sequencing of the ctxB (+) strains revealed that all isolates (El Tor strains) possessed the ctxB sequence of classical biotype allele known as El Tor variant strains. No class 1 or 2 integrons were detected among the isolates which indicate that in spite of high rate of resistance, integrons do not play an important role in V. cholerae resistance. All isolates were chloramphenicol sensitive all of which showed resistance to tetracycline and harbored the tetB resistance gene. PFGE analysis showed identical pulsotypes indicative of clonal dissemination of a single V. cholerae strain among the patients under study. Clonal cholera outbreak in boarder cities is alarming due to fear of import and spread of V. cholerae strains from out of the country which may lead to more spreading epidemics.