Cardiomyopathy (particularly dilated cardiomyopathy (DCM)) significantly contributes to development and progression of heart failure (HF), and inflammatory factors further deteriorate the symptoms. Morphological and functional defects of the heart in doxorubicin (DOX)-induced cardiomyopathy (cardiotoxicity) are similar to those of DCM. We used anagonist of PGC-1α (PPAR (peroxisome proliferator-activated receptor-gamma)-γ coactivator-1α) that is considered as the ‘master regulator’ of mitochondrial biogenesis with an aim to rescue the DOX-induced deleterious effects on the heart. Forty male C57BL/6J mice (8 weeks old) were divided in four groups, Control, DOX, ZLN005, and ZLN005 + DOX (n = 10 each group). The DOX-induced (10 mg/kg, single dose) cardiomyopathy mimics a DCM-like phenotype with marked morphologic alteration in cardiac tissue and functional derangements. Significant increased staining was observed for Masson Trichrome/Picrosirius red and α-Smooth Muscle Actinin (α-SMA) that indicated enhanced fibrosis in the DOX group compared to the control that was attenuated by (peroxisome proliferator-activated receptor-gamma (PPAR-γ) coactivator) (PGC)-1α (alpha) agonist (four doses of 2.5 mg/kg/dose; cumulative dose = 10 mg/kg). Similarly, elevated expression of necroptosis markers along with enhanced oxidative stress in the DOX group were alleviated by PGC-1α agonist. These data collectively suggested the potent therapeutic efficacy of PGC-1α agonist in mitigating the deleterious effects of DOX-induced cardiomyopathy, and it may be targeted in developing the future therapeutics for the management of DCM/HF.
India has the largest Buffalo population in the world, with every household in rural India owning buffaloes depending upon daily milk requirement – dairy farmers can own between 10 to 70 buffaloes. The health of Indian buffaloes is of economic importance since India is one of the largest buffalo meat exporters in the world, and Indian Buffalo semen is sold in the USA for breeding purposes. However, National Control Program on brucellosis is only active in South India and in Panjab (a North Indian state with high human brucellosis incidence). Our aim was to assess the knowledge and practices of the buffalo keepers of Delhi that make them susceptible to brucellosis. Amongst all the 11 districts of Delhi, there was 0% awareness about brucellosis and also about the S19 vaccine as the buffalo keepers had never heard of S19 vaccine which is available at minimal cost from Indian Veterinary Research Institute, Bareilly, India. Majority of the respondents drink raw milk, sleep in cattle sheds, do not isolate sick cattle, do not test buffaloes blood for any disease before purchasing them, apply intrauterine medication with bare hands to buffalo after abortion of foetus, never clean their cattle sheds with a disinfectant and believe that they can only acquire skin infections from cattle. All of these habits make them prone to brucellosis. While about 20 to 27% of respondents reported a history of abortions and retained placenta, disposed of the placenta with bare hands, and applied raw milk on cracked lips. It was surprising to note that majority of them never reared small ruminants like sheep and goat with buffaloes or Bos species as they were aware of the rapid spread of disease from small to big ruminants. We found that buffalo keepers were ignorant of brucellosis, its causative agent, relevant vaccines and that they also involved in high-risk activities. As such, our findings highlight a need for buffalo keepers to be better educated via several awareness camps to minimize human exposure to Brucella in Delhi.
Melittin is a major active ingredient of the bee venom produced by honeybees (Apis mellifera) that exerts various biological effects, such as anti-inflammatory, anti-tumor, anti-microbial, and antioxidant. The role of melittin in modulating melanin production by melanocytes is not known. Therefore, the present study aimed to study the effect of melittin on melanin production by human melanocytes along with its antioxidant status. Cultured human melanocytes were treated with melittin in a dose- and time-dependent manner, followed by the study of the cell viability, cell proliferation, and total melanin content. The effects of melittin in combination with narrow-band ultraviolet B (NB-UVB) on the total melanin content, melanocyte dendricity, oxidative stress, and the expression of genes associated with melanogenesis were investigated. An increased melanin content was observed with a low dose of melittin (LDM) (alone or in combination with NB-UVB), and there was a corresponding increase in the tyrosinase activity, melanocyte dendricity, and melanogenesis-associated genes. The present study concluded that LDM alone or LDM (+NB-UVB) can induce melanin synthesis by increasing the tyrosinase activity in melanocytes by limiting the oxidative stress, and this may be therapeutically exploited as an adjuvant therapy for vitiligo.