Variable Virulence and Efficacy of BCG Vaccine Strains in Mice and Correlation With Genome Polymorphisms.

Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. However, BCG is not an ideal vaccine and has two major limitations: BCG exhibits highly variable effectiveness against the development of TB both in pediatric and adult populations and can cause disseminated BCG disease in immunocompromised individuals. BCG comprises a number of substrains that are genetically distinct. Whether and how these genetic differences affect BCG efficacy remains largely unknown. In this study, we performed comparative analyses of the virulence and efficacy of 13 BCG strains, representing different genetic lineages, in SCID and BALB/c mice. Our results show that BCG strains of the DU2 group IV (BCG-Phipps, BCG-Frappier, BCG-Pasteur, and BCG-Tice) exhibit the highest levels of virulence, and BCG strains of the DU2 group II (BCG-Sweden, BCG-Birkhaug) are among the least virulent group. These distinct levels of virulence may be explained by strain-specific duplications and deletions of genomic DNA. There appears to be a general trend that more virulent BCG strains are also more effective in protection against Mycobacterium tuberculosis challenge. Our findings have important implications for current BCG vaccine programs and for future TB vaccine development.

Zuogui-Jiangtang-Yishen decoction prevents diabetic kidney disease: Intervene pyroptosis induced by trimethylamine n-oxide through the mROS-NLRP3 axis.

BACKGROUND: Nowadays, diabetic kidney disease (DKD) has become one of the most threatening to the end-stage renal diseases, and the early prevention of DKD is inevitable for Diabetes Mellitus (DM) patients. AIMS: Pyroptosis, a programmed cell death that mediates renal inflammation induced early renal injury. The trimethylamine n-oxide (TMAO) was also an independent risk factor for renal injury. Here, the associations between TMAO-induced pyroptosis and pathogenesis of DKD were studied, and the potential mechanism of Zuogui-Jiangtang-Yishen (ZGJTYS) decoction to prevent DKD was further investigated. METHOD: Using Goto-Kakizaki (GK) rats to establish the early DKD models. The 16S-ribosomal RNA (16S rRNA) sequencing, fecal fermentation and UPLC-MS targeted metabolism techniques were combined to explore the changes of gut-derived TMAO level under the background of DKD and the effects of ZGJTYS. The proximal convoluted tubule epithelium of human renal cortex (HK-2) cells was adopted to explore the influence of pyroptosis regulated by TMAO. RESULTS: It was demonstrated that ZGJTYS could prevent the progression of DKD by regulating glucolipid metabolism disorder, improving renal function and delaying renal pathological changes. In addition, we illustrated that gut-derived TMAO could promote DKD by activating the mROS-NLRP3 axis to induce pyroptosis. Furthermore, besides interfering with the generation of TMAO through gut microbiota, ZGJTYS inhibited TMAO-induced pyroptosis with a high-glucose environment and the underlying mechanism was related to the regulation of mROS-NLRP3 axis. CONCLUSION: Our results suggested that ZGJTYS inhibited the activation of pyroptosis by gut-derived TMAO via the mROS-NLRP3 axis to prevent DKD.

Recurrent herpes zoster in a rheumatoid arthritis patient treated with tofacitinib: A case report and review of the literature.

BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor that is currently approved by the United States Food and Drug Administration for the treatment of rheumatoid arthritis (RA). Varicella zoster virus reactivation leading to herpes zoster (HZ) is an adverse effect of this drug; however, recurrent HZ at the same site is a rare clinical condition. CASE SUMMARY: A 70-year-old female RA patient had undergone 1-year of tofacitinib treatment (10 mg daily). About 1 mo after initiation of oral tofacitinib, she developed blisters on the left flank and abdomen and was diagnosed with HZ; antiviral therapy with acyclovir was resolutory. However, 5 d prior to presentation at our hospital, erythema and blisters with severe pain recurred at the same site. Small clustered blisters and bullous were visible on the left lumbar abdomen and perineum, with a pain score of 8 (visual analogue scale). Antiviral, nutritional supplement, analgesic and other treatments led to healing but over an atypically long period (approximately 26 d, vs approximately 1 wk). HZ is a common and serious adverse reaction of JAK inhibitors, but it rarely recurs. Our patient's experience of HZ recurrence at the same site, with a wider affected area, more severe pain and longer healing period, is inconsistent with previous reports. CONCLUSION: Same-anatomical site HZ recurrence may occur during oral tofacitinib treatment, with more severe clinical manifestations than in the initial occurrence.