Quadruped Gait and Regulation of Apoptotic Factors in Tibiofemoral Joints following Intra-Articular rhPRG4 Injection in Prg4 Null Mice.

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome leads to diarthrodial joint arthropathy and is caused by the absence of lubricin (proteoglycan 4-PRG4), a surface-active mucinous glycoprotein responsible for lubricating articular cartilage. In this study, mice lacking the orthologous gene Prg4 served as a model that recapitulates the destructive arthrosis that involves biofouling of cartilage by serum proteins in lieu of Prg4. This study hypothesized that Prg4-deficient mice would demonstrate a quadruped gait change and decreased markers of mitochondrial dyscrasia, following intra-articular injection of both hindlimbs with recombinant human PRG4 (rhPRG4). Prg4-/- (N = 44) mice of both sexes were injected with rhPRG4 and gait alterations were studied at post-injection day 3 and 6, before joints were harvested for immunohistochemistry for caspase-3 activation. Increased stance and propulsion was shown at 3 days post-injection in male mice. There were significantly fewer caspase-3-positive chondrocytes in tibiofemoral cartilage from rhPRG4-injected mice. The mitochondrial gene Mt-tn, and myosin heavy (Myh7) and light chains (Myl2 and Myl3), known to play a cytoskeletal stabilizing role, were significantly upregulated in both sexes (RNA-Seq) following IA rhPRG4. Chondrocyte mitochondrial dyscrasias attributable to the arthrosis in CACP may be mitigated by IA rhPRG4. In a supporting in vitro crystal microbalance experiment, molecular fouling by albumin did not block the surface activity of rhPRG4.

Efficacy of marine cyanobacterium Oxynema thaianum ALU PBC5 against multi drug resistant Gram negative pathogens.

AIM: Emergence of extended antibiotic resistance among several human bacterial pathogens often leads to the failure of existing antibiotics to treat bacterial infections worldwide. Hence, the present study is aimed to explore antibacterial activity of marine cyanobacterium against MDR pathogens. METHODS AND RESULTS: The cyanobacterial samples were collected and isolated from Thondi Palk Strait region. The isolate was subjected to polarity based solvent extraction and checked for their antibacterial activity against test bacterial pathogens. The active principles from chloroform extract of Oxynema thaianum (CEOT) were partially purified through thin layer chromatography (TLC). The active principle with highest activity was further characterized by FTIR, high performance liquid chromatography (HPLC) and gas chromatography mass spectrometry (GC-MS) analysis. Among the eight extracts tested, CEOT showed effective zone of clearance against ESBL producing Escherichia coli and Klebsiella pneumoniae in disc diffusion method. In TLC, all the purified five fractions were eluted and tested for their antibacterial activity against test pathogens. The third fraction showing maximum activity was subjected to HPLC analysis for checking its purity. In GC-MS analysis, 9-octadecenoic acid, methyl ester and hexadecanoic acid were identified as the major chemical compounds. CONCLUSION: Hence, the present study was concluded that O. thaianum ALU PBC5 is a promising agent to treat ESBL producing MDR bacterial pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the pioneer study on screening and isolation of bioactive compounds from the marine cyanobacteria against MDR pathogens such as E. coli and K. pneumoniae. Here, 9-octadecenoic acid, methyl ester and hexadecanoic acid were identified as the major chemical compounds through TLC, FTIR, HPLC and GC-MS. From this screen, we identified the bioactive compounds against ESBL producing multidrug resistant pathogens such as E. coli and K. pneumoniae.