Role of CXCR5+ CD8+ T cells in human hepatitis B virus infection.

The replication of HBV in hepatocytes can be effectively inhibited by lifelong antiviral therapy. Because of the long-term presence of HBV reservoirs, the virus rebound frequently occurs once the treatment is stopped, which poses a considerable obstacle to the complete removal of the virus. In terms of gene composition, regulation of B cell action and function, CXCR5+ CD8+ T cells are similar to CXCR5+ CD4+ T follicular helper cells, while these cells are characterized by elevated programmed cell death 1 and cytotoxic-related proteins. CXCR5+ CD8+ T cells are strongly associated with progression in inflammatory and autoimmune diseases. In addition, CXCR5 expression on the surface of CD8+ T cells is mostly an indicator of memory stem cell-like failure in progenitor cells in cancer that are more responsive to immune checkpoint blocking therapy. Furthermore, the phenomena have also been demonstrated in some viral infections, highlighting the duality of the cellular immune response of CXCR5+ CD8+ T cells. This mini-review will focus on the function of CXCR5+ CD8+ T cells in HBV infection and discuss the function of these CD8+ T cells and the potential of associated co-stimulators or cytokines in HBV therapeutic strategies.

Inhibition of HSPA8 by rifampicin contributes to ferroptosis via enhancing autophagy.

BACKGROUND AND AIM: Rifampicin is the most common pathogenic factor in anti-tuberculosis drug-induced liver injury (AT-DILI), the mechanisms that it promotes hepatocyte damage in AT-DILI are not yet to be thoroughly elucidated. In this study, we investigated the potential molecular mechanisms for ferroptosis involving rifampicin hepatotoxicity. METHODS: Animal and cell injury models of rifampicin were constructed, and the toxicity of rifampicin was assessed by physicochemical staining and cell viability assay. Next, flow cytometry was employed to detect changes in ferroptosis-related markers, and Western blotting was used to detect protein expression. Then, the important role of autophagy and ferroptosis was verified with small molecule compound intervention. RESULTS: We found that ferritinophagy-induced ferroptosis participates in the toxicity of rifampicin, and the mechanism is that rifampicin precisely activates high-throughput autophagy, which leads to the massive degradation of ferritin and the increase of free iron. Moreover, rifampicin exhibited conspicuous inhibition of Human 71 kDa heat shock cognate protein (HSPA8) that is intimately associated with Microtubule-associated protein light chain 3 isoform B (LC3B) expression, in turn, HSPA8 inducer attenuated intracellular autophagy flux. Of note, inducing HSPA8 or inhibition of autophagy and ferroptosis considerably relieved the hepatotoxicity of rifampicin in mouse model. CONCLUSIONS: The present study highlights the crucial roles of the HSPA8 and autophagy in ferroptotic cell death driving by rifampicin, particularly illumines multiple promising regulatory nodes for therapeutic interventions in diseases involving AT-DILI.

Effects of growth hormone/estrogen/androgen on COVID-19-type proinflammatory responses in normal human lung epithelial BEAS-2B cells.

BACKGROUND: COVID-19 is a disease caused by SARS-CoV-2, which can cause mild to serious infections in humans. We aimed to explore the effect of growth hormone (GH)/estrogen/androgen in normal human lung epithelial BEAS-2B cells on COVID-19-type proinflammatory responses. METHODS: A BEAS-2B COVID-19-like proinflammatory cell model was constructed. After that, the cells were treated with GH, 17ß-estradiol (E2), and testosterone (Tes) for 24 h. CCK-8 assays were utilized to evaluate cell viability. The mRNA expression of ACE2, AGTR1, TMRRSS2, and ISG15 and the protein expression of ACE2, AGTR1, TMRRSS2, and ISG15 were measured by qRT‒PCR and Western blotting, respectively. ELISAs were performed to determine IL-6, MCP-1, MDA and SOD expression. Flow cytometry was used to measure ROS levels. Finally, MAPK/NF-κB pathway-related factor expression was evaluated. RESULTS: The COVID-19-type proinflammatory model was successfully constructed, and 1000 ng/mL RBD treatment for 24 h was selected as the condition for the model group for subsequent experiments. After RBD treatment, cell viability decreased, the mRNA expression of ACE2, AGTR1, TMRRSS2, and ISG15 and the protein expression of ACE2, AGTR1, TMRRSS2, and ISG15 increased, IL-6, MCP-1, MDA and ROS levels increased, and MDA levels decreased. The mRNA levels of MAPK14 and RELA increased, but the protein levels did not change significantly. In addition, phospho-MAPK14 and phospho-RELA protein levels were also increased. Among the tested molecules, E2 had the most pronounced effect, followed by GH, while Tes showed the opposite effect. CONCLUSION: GH/E2 alleviated inflammation in a COVID-19-type proinflammatory model, but Tes showed the opposite effect.

Lumbar infection caused by Mycobacterium paragordonae: A case report.

BACKGROUND: Mycobacterium paragordonae (M. paragordonae), a slow-growing, acid-resistant mycobacterial species, was first isolated from the sputum of a lung infection patient in South Korea in 2014. Infections caused by M. paragordonae are rare. CASE SUMMARY: Herein, we report the case of a 53-year-old patient who presented with fever and low back pain. Lumbar nuclear magnetic resonance imaging revealed the destruction of the lumbar vertebra with peripheral abscess formation. After anti-infective and diagnostic anti-tuberculosis treatment, the patient had no further fever, but the back pain was not relieved. Postoperatively, the necrotic material was sent for pathological examination, and all tests related to tuberculosis were negative, but pus culture suggested nontuberculous mycobacteria. The necrotic tissue specimens were subjected to metagenomic next-generation sequencing, which indicated the presence of M. paragordonae. Finally, the infecting pathogen was identified, and the treatment plan was adjusted. The patient was in good condition during the follow-up period. CONCLUSION: M. paragordonae, a rare nontuberculous mycobacterium, can also cause spinal infections. In the clinic, it is necessary to identify nontuberculous mycobacteria for spinal infections similar to Mycobacterium tuberculosis.

Role of eosinophils in the diagnosis and prognostic evaluation of COVID-19.

Severe acute respiratory syndrome coronavirus 2 is responsible for the coronavirus disease 2019 (COVID-19) epidemic, which has severely affected global public health security. However, the diagnosis and treatment of the disease need further exploration. Therefore, this retrospective analysis was conducted on multiple indicators of peripheral blood in patients with COVID-19 to determine the role of leukocytes, lymphocytes, and eosinophils in the diagnosis and prognostic evaluation of COVID-19. Baseline information and clinical records of 40 patients were collected, including demographic data, disease status, medication, and laboratory routine. The correlation between the inspection indicators and disease classification, as well as prognostic factors, was analyzed. Decreased eosinophils were detected in 33 out of 40 patients with COVID-19 on admission, while lymphocytes and eosinophils were inversely related to the severity of the disease, according to the Spearman's correlation coefficient. Thus, it could be deduced that eosinophils have better sensitivity for the diagnosis of COVID-19 and play a major role similar to lymphocytes in assessing the prognosis of patients.