Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features

<p>Abstract</p> <p>Background</p> <p>Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL); however, osteonecrosis of the jaw (ONJ) is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP)-related and denosumab (anti-RANKL antibody)-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC)-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL) in ONJ-altered and healthy periodontal tissue.</p> <p>Methods</p> <p>Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each) to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels.</p> <p>Results</p> <p>Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p < 0.05) expression in ONJ-adjacent periodontal tissue. ONJ tissue also exhibited decreased relative gene expression for Msx-1 (p < 0.03) and RANKL (p < 0.03) and increased BMP-2/4 expression (p < 0.02) compared to control.</p> <p>Conclusions</p> <p>These results explain the sclerotic and osteopetrotic changes of periodontal tissue following BP application and substantiate clinical findings of BP-related impaired remodeling specific to periodontal tissue. RANKL suppression substantiated the clinical finding of impaired bone remodelling in BP- and aRANKL-induced ONJ-affected bone structures. Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to maxillofacial tissue.</p

Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019

BACKGROUND: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. METHODS: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. FINDINGS: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. INTERPRETATION: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. FUNDING: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38)

Assessment of the Antimicrobial Activity of Lactic Acid Bacteria from Sorghum Slurry on Clinical Strains of Diarrhoeagenic Escherichia coli

Background:&nbsp;Sorghum is a nutrient-rich grain ground into flour to make different types of delicacies, and it has been reported to possess probiotic potentials. Objective:&nbsp;To assess the antimicrobial activity of&nbsp;Lactobacillus plantarum&nbsp;obtained from sorghum slurry on strains of enteropathogenic&nbsp;Escherichia coli&nbsp;from cases of diarrhoea. Methods:&nbsp;A total of 36 samples of wet-milled sorghum slurry and liquor pH were obtained and cultured on MRSA and were, after that, biochemically characterized for&nbsp;Lactobacillus plantarum,&nbsp;which was tested by agar well diffusion against 15 strains of&nbsp;Escherichia coli&nbsp;isolated from cases of diarrhoea. Results:&nbsp;Microbiological analysis of the 36 samples of sorghum explored produced 15 isolates of&nbsp;Lactobacillus plantarum. A progressive increase in acidity in relation to an increase in the period of fermentation was observed. Ninety-five per cent of the&nbsp;Escherichia coli&nbsp;strains showed resistance against some standard antibiotics. At the same time, the isolates of&nbsp;Lactobacillus plantarum&nbsp;obtained inhibited isolates of diarrhoeagenic&nbsp;Escherichia coli&nbsp;tested, showing potential usefulness of the sorghum slurry as a probiotic. Conclusion:&nbsp;The inhibitory activity of&nbsp;Lactobacillus plantarum&nbsp;isolated from sorghum slurry showed antimicrobial potentials that could be used for therapeutic purposes in treating diarrhoea caused by&nbsp;&nbsp;&nbsp;Escherichia coli,&nbsp;pending further investigation

Effect of sole maize and maize –lablab silage on the ruminal volatile fatty acids (VFAS) of grazing calves in the dry season

Silages of sole maize and mixtures of maize-lablab were made at harvest in plastic bags. The experimental Unit consists of twelve cross-bred yearling bulls (White Fulani x N’dama) calves weighing 71-72kg and were randomly allotted to three dietary treatments: Grazing + sole maize silage, Grazing + mixtures of maize-lablab silage and Unsupplemented grazing as control. The experimental design was a completely randomized design and lasted 84days. Silage diets were given between 07:30 and 11:00 hours daily before grazing. Rumen fluid was collected at the end of the study to evaluate the co-efficient of ruminal fluid. The crude protein content in sole maize silage was half of that in mixture of maize-lablab silage. Inclusion of lablab in maize stover silage increased the mineral content as well as the lignin fraction. The mean pH value of sole maize silage (3.80) was less (P &lt; 0.05) than 4.25 obtained with addition of lablab. The buffering capacity (5.37%) of sole maize silage significantly (P &lt; 0.05) increased to 5.71% in mixture of maize-lablab silage. Lactic acid contents differed was influenced significantly (P &lt; 0.05) with a mean value of 8.4% and 8.5% respectively in the sole maize silage and with lablab inclusion. Total volatile fatty acid (VFA) ranged from 56.7 μmoles/ml in calves without supplementation to 95.2 μmoles/ml in the calves fed mixture of maize-lablab silage. Mixture of Maize-lablab silage had the highest values for all the minerals determined in the feed materials while sole maize had the least. It was concluded from this trial, that forage legumes are relatively good sources of degradable nitrogen and fermentable energy, so their inclusion in the diet is likely to increase the rumen population of cellulolytic microbes and also proves that, mixture of maize-lablab silage could be used as supplement to enhance the growth and survival of calves during the dry season, when animal feeds are relatively scarce.Keywords: Grazing calves; maize stover; natural pasture; volatile fatty acid