HIV-1 Infection Promotes Cholesterol Aggregation by Inducing miR-33b-5p to Suppress ABCA1 Expression.

MicroRNAs play an important role in the interaction between viruses and hosts. In this study, we found that the expression level of miR-33b-5p was markedly increased in human immunodeficiency virus type 1 (HIV-1)-infected cell lines and the serum of person with HIV-1. Further investigation revealed that the level of ATP-binding cassette transporter (ABCA1), which transports cholesterol between intracellular and extracellular compartments to maintain cholesterol homeostasis, was reduced in HIV-1-infected target cells, as the target gene of miR-33b-5p. Furthermore, HIV-1 infection stimulated abnormal lipid transport in macrophages, resulting in lipid accumulation in cells. These changes can be reversed by an miR-33b-5p inhibitor. We discovered a mechanism through which HIV-1 infection caused miR-33b-5p to target ABCA1 and caused aberrant lipid transport, providing a novel method for diagnosing and treating poor lipid metabolism in person with HIV-1.

Effectiveness and Controversy of Convalescent Plasma Therapy for Coronavirus Disease 2019 Patients.

Since the coronavirus disease 2019 (COVID-19) began to spread, it remains pandemic worldwide. The European Medicines Agency's human medicines committee and Food and Drug Administration have only granted a conditional marketing authorization for remdesivir to treat COVID-19. It is essential to apply other valuable treatments. Convalescent plasma (CP), donated by persons who have recovered from COVID-19, is the cellular component of blood that contains specific antibodies. Therefore, to determine the feasibility of CP for COVID-19, the effectiveness and controversy are discussed in depth here. It is suggested that CP plays a certain role in the treatment of COVID-19. As a treatment, it may have its own indications and contraindications, which need to be further discussed. Meanwhile, it is critical to establish a standard procedure for treatment from CP collection, preservation, transport, to transfusion, and conduct some large sample randomized controlled trials to confirm the transfusion dosage, appropriate time, frequency, and actively prevent adverse outcomes that may occur.

Human umbilical cord mesenchymal stem cell transfusion in immune non-responders with AIDS: a multicenter randomized controlled trial.

We examined the safety and efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) infusion for immune non-responder (INR) patients with chronic HIV-1 infection, who represent an unmet medical need even in the era of efficient antiretroviral therapy (ART). Seventy-two INR patients with HIV were enrolled in this phase II randomized, double-blinded, multicenter, placebo-controlled, dose-determination trial (NCT01213186) from May 2013 to March 2016. They were assigned to receive high-dose (1.5 × 106/kg body weight) or low-dose (0.5 × 106/kg body weight) hUC-MSC, or placebo. Their clinical and immunological parameters were monitored during the 96-week follow-up study. We found that hUC-MSC treatment was safe and well-tolerated. Compared with baseline, there was a statistical increase in CD4+ T counts in the high-dose (P < 0.001) and low-dose (P < 0.001) groups after 48-week treatment, but no change was observed in the control group. Kaplan-Meier analysis revealed a higher cumulative probability of achieving an immunological response in the low-dose group compared with the control group (95.8% vs. 70.8%, P = 0.004). However, no significant changes in CD4/CD8+ T counts and CD4/CD8 ratios were observed among the three groups. In summary, hUC-MSC treatment is safe. However, the therapeutic efficacy of hUC-MSC treatment to improve the immune reconstitution in INR patients still needs to be further investigated in a large cohort study.

SOX5 Regulates Cell Proliferation, Apoptosis, Migration and Invasion in KSHV-Infected Cells.

Kaposi's sarcoma (KS) originates from vascular endothelial cells, with KS-associated herpesvirus (KSHV) as the etiological agent. SRY-box transcription factor 5 (SOX5) plays different roles in various types of cancer, although its role in KS remains poorly understood. In this study, we identified the role of SOX5 in KS tissues and KSHV-infected cells and elucidated the molecular mechanism. Thirty-two KS patients were enrolled in this study. Measurement of SOX5 mRNA and protein levels in human KS tissues and adjacent control tissues revealed lower levels in KS tissues, with KS patients having higher SOX5 level in the early stages of the disease compared to the later stages. And SOX5 mRNA and protein was also lower in KSHV-infected cells (iSLK-219 and iSLK-BAC) than normal cells (iSLK-Puro). Additionally, SOX5 overexpression inhibited cell proliferation and promoted apoptosis and decreased KSHV-infected cell migration and invasion. Moreover, we found that SOX5 overexpression suppressed the epithelial-to-mesenchymal transition of KSHV-infected cells. These results suggest SOX5 is a suppressor factor during KS development and a potential target for KS treatment.

Kaposi's sarcoma-associated herpesvirus seropositivity is associated with type 2 diabetes mellitus: A case-control study in Xinjiang, China.

OBJECTIVE: To assess the potential relationship between Kaposi's sarcoma-associated herpesvirus (KSHV) infection and type 2 diabetes mellitus (DM-2) in Xinjiang, China. METHODS: A case-control study of consecutively included DM-2 patients and normal controls was conducted among the Uygur and Han populations in Xinjiang Uygur Autonomous Region, China. Blood samples were collected and KSHV seroprevalence, antibody titers, and viral load were investigated. Logistic regression analysis and multiple linear regression analysis were applied to explore determinants of the main outcome measures. RESULTS: A total of 324 patients with DM-2 and 376 normal controls were included. The seroprevalence of KSHV was 49.1% (95% confidence interval (CI) 43.6-54.5%) for diabetic patients and 23.7% (95% CI 19.4-28.0%) for the control group. After adjusting for variables of ethnicity, sex, body mass index, occupation, educational level, marital status, age, and smoking and alcohol consumption habits, the association between DM-2 and KSHV infection still existed (odds ratio (OR) 2.94, 95% CI 2.05-4.22), and the risk of KSHV infection increased with glucose concentration (OR 1.35, 95% CI 1.21-1.51). KSHV was more likely to express both the latent and lytic antigens in diabetic patients (latent: OR 3.27, 95% CI 2.25-4.75; lytic: OR 3.99, 95% CI 2.68-5.93). Antibody titers and viral load increased in patients with higher blood glucose levels (p<0.001). CONCLUSIONS: Patients with DM-2 have an elevated risk of KSHV infection. Both antibody titers and viral load increased with blood glucose levels.

Tolerable and curable treatment in HIV/HCV co-infected patients using anti-HCV direct antiviral agents: a real-world observation in China.

OBJECTIVE: No brand direct-acting antiviral agents (DAAs) are available for treatment of HIV-1/HCV co-infected patients in China. This study aimed to observe the therapeutic efficacy and safety of generic DAAs for affected Chinese patients. DESIGN: Real-world setting to elucidate whether DAAs were tolerated and effective in HIV-1/HCV co-infected patients. METHODS: 176 HIV-1/HCV co-infected patients received anti-HCV DAA treatment together with ART regimens for HIV infection. Among the 176 patients, 99 patients were treated with SOF + DCV ± RBV, 60 patients were treated with SOF + LDV ± RBV, and 17 patients received SOF + RBV ± Peg-IFN regimens, for 12 or 24 weeks, respectively. The primary endpoint was undetectable HCV RNA 12 weeks after therapy was completed (SVR12). Data pertaining to safety and adverse events were analyzed. RESULTS: 151/176 HIV-1/HCV co-infected patients finished the treatment and 12-week follow-up. SVR12 for the patients treated with regimens of SOF + DCV, SOF + DCV+RBV, SOF + Peg-IFN+RBV, SOF + RBV, SOF + LDV, and SOF + LDV+RBV for 12 or 24 weeks was 100% (75/75), 100% (11/11), 100% (14/14), 100% (2/2), 95.2% (40/42), and 100% (7/7), respectively. HIV-1/HCV co-infected patients with liver cirrhosis achieved well SRV12. Notably, there was no significant difference in adverse effects among patients with different baseline CD4+ T-cell count in those who received DAA regimens with or without Peg-IFN and RBV. CONCLUSION: We showed generic SOF + DCV and SOF + LDV regimens were well tolerated and with high efficiency. Patient's baseline CD4+ T-cell count did not exhibit significant difference in adverse effects.

Surveillance of HIV-1 drug resistance in Xinjiang: high prevalence of K103N in treatment-naïve individuals.

To identify transmitted and acquired HIV-1 drug resistance mutations in Xinjiang, China, we collected the peripheral blood of 50 treated and 50 treatment-naïve HIV-1-infected individuals in this region. We successfully amplified 36 reverse transcriptase and 42 protease gene sequences of HIV-1 from 51 individuals and identified mutations associated with resistance to reverse transcriptase (RT) and protease (PR) inhibitors (RTIs and PIs) according to Stanford Drug Resistance Database. Among the drug-treated individuals, the results showed that K103N in the RT region was the most frequent mutation, found in 67% (6/9) of the cases, followed by M184V with 56% (5/9). Five individuals had both nucleoside and non-nucleoside reverse transcriptase inhibitor resistance mutations after more than 12 months of treatment. Among the untreated individuals, 33% (9/27) were found to harbor drug resistance mutations in the RT gene. K103N occurred at the highest rate, accounting for 22% (6/27), followed by P225H (7%) and Y188L (4%). Neither of the two groups showed any major resistance mutations to PIs. Our study revealed that the prevalence of drug resistance was relatively high in Xinjiang and that K103N occurred at the highest rate. These results suggest that it is important to carry out HIV drug resistance testing, especially for the K103N mutation in the RT region, before and during the treatment process. This study may help to guide ART strategies in the Xinjiang region.

HIV/AIDS-related hyponatremia: an old but still serious problem.

Hyponatremia is the most common electrolyte disorder in hospitals. Many medical illnesses, including congestive heart failure, liver failure, renal failure and pneumonia, may be associated with hyponatremia. In addition, hyponatremia in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) was first reported in 1993. The evidence suggests that severe hyponatremia is associated with increased morbidity and mortality in human immunodeficiency virus (HIV)/AIDS patients; however, the incidence of hyponatremic syndrome in HIV/AIDS patients remains very high in clinical practice, as almost 40% of HIV/AIDS inpatients in Xinjiang, a developing region of China, are hyponatremic. A method for identifying the pathogenesis and therapeutic treatments for hyponatremia in HIV/AIDS patients is needed. This review focuses on the clinical and pathophysiological aspects of hyponatremia and highlights the causes, presentation and treatment recommendations for hyponatremic patients with HIV/AIDS.

Prevalence of Kaposi's sarcoma-associated herpesvirus in Uygur and Han populations from the Urumqi and Kashgar regions of Xinjiang, China.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the infectious etiologic agent associated with Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease. It has been shown that high KSHV prevalence and high incidence of both classic KS and AIDSassociated KS are found mostly among people of Uygur ethnicity in Xinjiang, while people of Han ethnicity in Xinjiang have a higher KSHV seroprevalence than those of other Han populations in mainland China. However, it is still unclear why there is such geographical and population variation in KSHV distribution in China. In this work, we focused on the populations in the Kashgar region and Urumqi area, where a total of 1294 research subjects were randomly selected to investigate the potential correlation between KSHV prevalence and different ethnicities in endemic areas of Xinjiang, and to determine risk factors that may affect KSHV infection rates or KS incidence. We identified a high seroprevalence of KSHV and high peripheral blood DNA infection in the general Uygur and Han populations in both Urumqi and Kashgar regions of Xinjiang, and determined that advancing age, low education level, and stationary population status affect KSHV infection rates. Further, KSHV-positive Uygur participants were shown to have higher prevalence of neutralizing antibodies and neutralizing antibody titers than KSHV-positive Han participants.

How intestinal bacteria can promote HIV replication.

Since the 1950s, researchers have gradually realized that the body's bacteria help fight infection by crowding out potential pathogens. In the past decades, scientists have even begun to see our microbiota as thick­and­thin allies. However, the influence of gut bacteria on HIV is largely unknown. Our review likely sheds light on the previously indistinct role of commensal microbiota in retroviral pathogenesis. The delicate yet critical balance between this enormous bacterial population and the gastrointestinal tract is gradually destroyed along with HIV incursion. The leakage into the systemic circulation of bacterial and byproducts such as lipopolysaccharide directly stimulates the innate immune system through toll­like receptors. As a result, toll­like receptor­4 activation provokes production of interleukin­10, which mediates immunological tolerance. Therefore, a solid deduction is that intestinal microbes may be involved in triggering of replication and transmission of HIV, just like other retroviruses.

Maltose, a promising osmotic agent in peritoneal dialysis solution.

Peritoneal dialysis has undergone considerable development from a technological point of view, and osmotic agent has played the essential role in peritoneal dialysis fluid. Because the most commonly used osmotic agent is glucose and icodextrin, there are some disadvantages related to the use of glucose-based solutions and icodextrin. So it is urgent to develop a new peritoneal dialysis osmotic agent. According to these characteristics of glucose and icodextrin, it is promising to explore a better osmotic agent of peritoneal dialysis solution which is able to allow maintenance of the maximum ultrafiltration gradient, and prevent toxicity or accumulation of unwanted substances in the blood, being non-toxic or less-toxic, furthermore the metabolite should not cause significant metabolic disturbance. Maltose may be one of promising osmotic agent and may put an important influence on development of peritoneal dialysis.