Multifaceted Actions of Succinate as a Signaling Transmitter Vary with Its Cellular Locations

Since the identification of succinate's receptor in 2004, studies supporting the involvement of succinate signaling through its receptor in various diseases have accumulated and most of these investigations have highlighted succinate's pro-inflammatory role. Taken with the fact that succinate is an intermediate metabolite in the center of mitochondrial activity, and considering its potential regulation of protein succinylation through succinyl-coenzyme A, a review on the overall multifaceted actions of succinate to discuss whether and how these actions relate to the cellular locations of succinate is much warranted. Mechanistically, it is important to consider the sources of succinate, which include somatic cellular released succinate and those produced by the microbiome, especially the gut microbiota, which is an equivalent, if not greater contributor of succinate levels in the body. Continue learning the critical roles of succinate signaling, known and unknown, in many pathophysiological conditions is important. Furthermore, studies to delineate the regulation of succinate levels and to determine how succinate elicits various types of signaling in a temporal and spatial manner are also required.

Oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw / 国际口腔科学杂志·英文版

Bacterial biofilms have emerged as potential critical triggers in the pathogenesis of bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) or BRONJ. BRONJ lesions have shown to be heavily colonized by oral bacteria, most of these difficult to cultivate and presents many clinical challenges. The purpose of this study was to characterize the bacterial diversity in BRONJ lesions and to determine host immune response. We examined tissue specimens from three cohorts (n=30); patients with periodontal disease without a history of BP therapy (Control, n=10), patients with periodontal disease having history of BP therapy but without ONJ (BP, n=5) and patients with BRONJ (BRONJ, n=15). Denaturing gradient gel electrophoresis of polymerase chain reaction (PCR)-amplified 16S rRNA gene fragments revealed less bacterial diversity in BRONJ than BP and Control cohorts. Sequence analysis detected six phyla with predominant affiliation to Firmicutes in BRONJ (71.6%), BP (70.3%) and Control (59.1%). Significant differences (P<0.05) in genera were observed, between Control/BP, Control/BRONJ and BP/BRONJ cohorts. Enzyme-linked immunosorbent assay (ELISA) results indicated that the levels of myeloperoxidase were significantly lower, whereas interleukin-6 and tumor necrosis factor-alpha levels were moderately elevated in BRONJ patients as compared to Controls. PCR array showed significant changes in BRONJ patients with downregulation of host genes, such as nucleotide-binding oligomerization domain containing protein 2, and cathepsin G, the key modulators for antibacterial response and upregulation of secretory leukocyte protease inhibitor, proteinase 3 and conserved helix-loop-helix ubiquitous kinase. The results suggest that colonization of unique bacterial communities coupled with deficient innate immune response is likely to impact the pathogenesis of ONJ.

Household Secondary Attack Rate in Gandhinagar district of Gujarat state from Western India

Objectives: Current retrospective study aims to evaluate household Secondary Attack Rate (SAR) of COVID-19 in Gandhinagar (rural) district of Gujarat, India. Methods: Line-listing of 486 laboratory-confirmed patients, tested between 28th March to 2nd July was collected, out of them 80 (15% of overall sample) cases were randomly selected. Demographic, clinical and household details of cases were collected through telephonic interview. During interview 28 more patients were identified from the same household and were added accordingly. So, study included 74 unrelated cluster of households with 74 primary cases and 386 close contacts. Results: SAR in household contacts of COVID-19 in Gandhinagar was 8.8%. Out of 108, 8 patients expired (7.4%), where higher mortality was observed in primary cases (9.5%) as compared to secondary cases (3%). Occupational analysis showed that majority of the secondary cases (88%) were not working and hence had higher contact time with patient. No out-of-pocket expenditure occurred in 94% of the patients, in remaining 6% average expenditure of 1,49,633INR (2027 USD) was recorded. Conclusions: Key observations from the study are 1) SAR of 8.8% is relatively low and hence home isolation of the cases can be continued 2) Primary case is more susceptible to fatal outcome as compared to secondary cases 3) Government has covered huge population of the COVID-19 patients under cost protection. However, more robust studies with larger datasets are needed to further validate the findings.