From Immunogen to COVID-19 vaccines: Prospects for the post-pandemic era.

The COVID-19 pandemic has affected millions of people and posed an unprecedented burden on healthcare systems and economies worldwide since the outbreak of the COVID-19. A considerable number of nations have investigated COVID-19 and proposed a series of prevention and treatment strategies thus far. The pandemic prevention strategies implemented in China have suggested that the spread of COVID-19 can be effectively reduced by restricting large-scale gathering, developing community-scale nucleic acid testing, and conducting epidemiological investigations, whereas sporadic cases have always been identified in numerous places. Currently, there is still no decisive therapy for COVID-19 or related complications. The development of COVID-19 vaccines has raised the hope for mitigating this pandemic based on the intercross immunity induced by COVID-19. Thus far, several types of COVID-19 vaccines have been developed and released to into financial markets. From the perspective of vaccine use in globe, COVID-19 vaccines are beneficial to mitigate the pandemic, whereas the relative adverse events have been reported progressively. This is a review about the development, challenges and prospects of COVID-19 vaccines, and it can provide more insights into all aspects of the vaccines.

From degenerative disease to malignant tumors: Insight to the function of ApoE.

Apolipoprotein E (ApoE) is a multifunctional protein involved in lipid transport and lipoprotein metabolism, mediating lipid distribution/redistribution in tissues and cells. It can also regulate inflammation and immune function, maintain cytoskeleton stability, and improve neural tissue Function. Due to genetic polymorphisms of ApoE (ε2, ε3, and ε4), its three common structural isoforms (ApoE2, ApoE3, ApoE4) are also associated with the risk of many diseases, especially degenerative diseases, such as vascular degenerative diseases including atherosclerosis (AS), coronary heart disease (CHD), and neurodegenerative disease like Alzheimer's disease (AD). The frequency of the ε4 allele and APOE variants were significantly higher than that of the ε2 and ε3 alleles in the patients with CHD or AD. In recent years, ApoE has frequently appeared in tumor research and become a tumor biomarker gradually. It has been found that ApoE is highly expressed in most solid tumor tissues, such as glioblastoma, gastric cancer, pancreatic ductal cell carcinoma, etc. Studies illustrated that ApoE could regulate the polarization changes of macrophages, participate in the construction of tumor immune microenvironment, regulate tumor inflammation and immune response and play a role in tumor progression, invasion, and metastasis. Of course, many functions of ApoE and its relationship with diseases are still under research. By reviewing the structure and function of ApoE from degeneration diseases to tumor neoplasms, we hope to better understand such a biomarker and further explore the value of ApoE in later studies.

Primary closure combined with C-tube drainage through cystic duct after laparoscopic common bile duct exploration is safe and feasible for patients.

Objective: Biliary duct management is of great significance after laparoscopic cholecystectomy (LC) combined with laparoscopic common bile duct exploration (LCBDE) in the treatment of cholecystolithiasis accompanied with common bile duct (CBD) stones. This study is to evaluate the safety and effectiveness of primary closure with C-tube drainage through cystic duct after LC + LCBDE. Methods: Through a retrospective study, 290 patients who underwent LC + LCBDE in our hospital from January 2019 to April 2022 were enrolled and divided into 2 groups. 143 patients underwent primary closure with C-tube drainage through cystic duct (C-tube group) and the other 147 patients underwent traditional T-tube drainage (T-tube group). Personal information, perioperative examinations, surgical results, and follow-up results were collected and analyzed. Results: There were no significant differences in the average age, gender, the mean of CBD diameters and the rate of comorbidities (acute cholecystitis, obstructive jaundice, acute pancreatitis and acute cholangitis) between the two groups (P > 0.05). Hospital stay, postoperative hospital stay were significantly shorter in the C-tube group than T-tube group (P < 0.05). In addition, the average time of placing and removal the drainage tubes was significantly less than those of the T-tube group (P < 0.05). This study also showed significant differences in the incidence of postoperative abdominal infection and soft tissue infection in the two groups (P < 0.05). There were no significant differences in the incidence of postoperative complications including cholangitis, bile duct stenosis, mortality in two groups. There were also no significant differences between the two groups of the recurrence of CBD stones, reoperation and readmition in 30 days during the median follow-up of 6 months. Conclusions: Compared with T tube drainage, patients with C-tube drainage after LC + LCBDE with primary closure of cystic duct recovered faster and had fewer complications. C-tube drainage is a safe and feasible treatment option for patients with cholecystolithiasis and choledocholithiasis.

Inhibition of PARP Potentiates Immune Checkpoint Therapy through miR-513/PD-L1 Pathway in Hepatocellular Carcinoma.

Background: The DNA repair enzyme poly(ADP-ribose) polymerase (PARP) is involved in DNA damage repair and cell death. However, the association between PARP's biological activities and the immune microenvironment in hepatocellular carcinoma (HCC) is unclear. The present study will explore whether combining a PARP inhibitor with anti-PD1 might improve the anti-HCC impact and explain how it works. Method: The PARP inhibitor olaparib was screened out of 867 drugs through Cell Counting Kit 8 (CCK-8) assay. The expression of PARP was verified through the TCGA and TISIDB databases. The impacts exerted by PARP inhibitor olaparib to HCC cells were assessed via wound healing, Transwell, and proliferation assay. In vivo, experiments were performed in a C57BL/6 mouse model to evaluate the function of PARP inhibitor olaparib combination with anti-PD1 in HCC and mice tumors were further detected by immunohistochemically staining. Result: Olaparib was selected as the research object on the basis of drug screening. The results of the TCGA and Human Protein Atlas databases revealed that PARP was significantly upregulated in carcinoma cell cluster of HCC tissues compared to normal tissues. Higher expression of PARP showed a poorer prognosis based on Kaplan-Meier Plotter. qRT-PCR experiments confirmed that olaparib could increase PD-L1 expression through inhibiting miR-513 in HCC cells. In vivo, experiment confirmed that the combination of olaparib and anti-PD1 could enhance the immunotherapy effect of HCC. Conclusion: The present study reveals that inhibition of PARP potentiates immune checkpoint therapy through the miR-513/PD-L1 pathway in HCC and the combination of PARP inhibitor olaparib and anti-PD1 is beneficial to HCC therapy.

miR-433 reduces cell viability and promotes cell apoptosis by regulating MACC1 in colorectal cancer.

MicroRNAs (miRNAs) are reported to have important roles in regulating the progression of numerous human cancers, although little is known regarding the role of miRNAs in colorectal cancer. The present study aimed to investigate the role of microRNA-433 (miR-433) in colorectal cancer. The expression levels of miR-433 and its target gene metastasis associated in colon cancer-1 (MACC1) in colorectal cancer tissues were evaluated using reverse transcription-quantitative polymerase chain reaction and western blotting. Furthermore, flow cytometry and MTT assays were used to examine the apoptosis, cell cycle distribution and viability of human colorectal cancer cells, and luciferase reporter and western blot assays were performed to verify the regulatory mechanism of miR-433 on MACC1. In addition, caspase-3 and caspase-9 expression were examined using western blotting. It was demonstrated that miR-433 expression was downregulated in colorectal cancer tissues and cell lines. Artificial upregulation of miR-433 in colorectal cancer cell lines using miR-433 mimics revealed that upregulation of miR-433 was able to reduce the viability and promote the apoptosis of colorectal cancer cells by downregulating MACC1. Taken together, these results suggested that miR-433 may have an important role in the pathogenesis of colorectal cancer.

Berberine ameliorates chronic kidney injury caused by atherosclerotic renovascular disease through the suppression of NFκB signaling pathway in rats.

BACKGROUND AND OBJECTIVES: Impaired renal function in atherosclerotic renovascular disease (ARD) may be the result of crosstalk between atherosclerotic renovascular stenosis and amplified oxidative stress, inflammation and fibrosis. Berberine (BBR) regulates cholesterol metabolism and exerts antioxidant effects. Accordingly, we hypothesized that BBR treatment may ameliorate ARD-induced kidney injury through its cholesterol-lowering effect and also suppression of the pathways involved in oxidative stress, inflammation and NFκB activation. METHODS: Male rats were subjected to unilateral renal artery stenosis with silver-irritant coil, and then fed with 12-week hypercholesterolemic diet. Rats with renal artery stenosis were randomly assigned to two groups (n = 6 each) - ARD, or ARD+BBR - according to diet alone or in combination with BBR. Similarly, age-matched rats underwent sham operation and were also fed with hypercholesterolemic diet alone or in combination with BBR as two corresponding controls. Single-kidney hemodynamic metrics were measured in vivo with Doppler ultrasound to determine renal artery flow. The metrics reflecting hyperlipidemia, oxidative stress, renal structure and function, inflammation and NFκB activation were measured, respectively. RESULTS: Compared with control rats, ARD rats had a significant increase in urinary albumin, plasma cholesterol, LDL and thiobarbituric acid reactive substances (TBARS) and a significant decrease in SOD activity. When exposed to 12-week BBR, ARD rats had significantly lower levels in blood pressure, LDL, urinary albumin, and TBARS. In addition, there were significantly lower expression levels of iNOS and TGF-ß in the ARD+BBR group than in the ARD group, with attenuated NFκB-DNA binding activity and down-regulated protein levels of subunits p65 and p50 as well as IKKß. CONCLUSIONS: We conclude that BBR can improve hypercholesterolemia and redox status in the kidney, eventually ameliorating chronic renal injury in rats with ARD, and that BBR can act against proinflammatory and profibrotic responses through suppression of the NFκB signaling pathway.