Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Many of vitamin A’s functions are executed through retinoic acids that activate transcriptional networks controlled by retinoic acid receptors (RARs) and retinoid X receptors (RXRs).The liver plays a central role in vitamin A metabolism: (1) it produces bile supporting efficient intestinal absorption of fat-soluble nutrients like vitamin A; (2) it produces retinol binding protein 4 (RBP4) that distributes vitamin A, as retinol, to peripheral tissues; and (3) it harbors the largest body supply of vitamin A, mostly as retinyl esters, in hepatic stellate cells (HSCs). In times of inadequate dietary intake, the liver maintains stable circulating retinol levels of approximately 2 μmol/L, sufficient to provide the body with this vitamin for months. Liver diseases, in particular those leading to fibrosis and cirrhosis, are associated with impaired vitamin A homeostasis and may lead to vitamin A deficiency. Liver injury triggers HSCs to transdifferentiate to myofibroblasts that produce excessive amounts of extracellular matrix, leading to fibrosis. HSCs lose the retinyl ester stores in this process, ultimately leading to vitamin A deficiency. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is a spectrum of conditions ranging from benign hepatic steatosis to non-alcoholic steatohepatitis (NASH); it may progress to cirrhosis and liver cancer. NASH is projected to be the main cause of liver failure in the near future. Retinoic acids are key regulators of glucose and lipid metabolism in the liver and adipose tissue, but it is unknown whether impaired vitamin A homeostasis contributes to or suppresses the development of NAFLD. A genetic variant of patatin-like phospholipase domain-containing 3 (PNPLA3-I148M) is the most prominent heritable factor associated with NAFLD. Interestingly, PNPLA3 harbors retinyl ester hydrolase activity and PNPLA3-I148M is associated with low serum retinol level, but enhanced retinyl esters in the liver of NAFLD patients. Low circulating retinol in NAFLD may therefore not reflect true “vitamin A deficiency”, but rather disturbed vitamin A metabolism. Here, we summarize current knowledge about vitamin A metabolism in NAFLD and its putative role in the progression of liver disease, as well as the therapeutic potential of vitamin A metabolites.

Systemic retinol (vitamin A) homeostasis is controlled by the liver, involving close collaboration between hepatocytes and hepatic stellate cells (HSCs). Genetic variants in retinol metabolism (PNPLA3 and HSD17B13) are associated with non-alcoholic fatty liver disease (NAFLD) and disease progression. Still, little mechanistic details are known about hepatic vitamin A metabolism in NAFLD, which may affect carbohydrate and lipid metabolism, inflammation, oxidative stress and the development of fibrosis and cancer, e.g. all risk factors of NAFLD. Here, we analyzed vitamin A metabolism in 2 mouse models of NAFLD; mice fed a high-fat, high-cholesterol (HFC) diet and Leptinob mutant (ob/ob) mice. Hepatic retinol and retinol binding protein 4 (RBP4) levels were significantly reduced in both mouse models of NAFLD. In contrast, hepatic retinyl palmitate levels (the vitamin A storage form) were significantly elevated in these mice. Transcriptome analysis revealed a hyperdynamic state of hepatic vitamin A metabolism, with enhanced retinol storage and metabolism (upregulated Lrat, Dgat1, Pnpla3, Raldh’s and RAR/RXR-target genes) in fatty livers, in conjunction with induced hepatic inflammation (upregulated Cd68, Tnfα, Nos2, Il1β, Il-6) and fibrosis (upregulated Col1a1, Acta2, Tgfβ, Timp1). Autofluorescence analyses revealed prominent vitamin A accumulation in hepatocytes rather than HSC in HFC-fed mice. Palmitic acid exposure increased Lrat mRNA levels in primary rat hepatocytes and promoted retinyl palmitate accumulation when co-treated with retinol, which was not detected for similarly-treated primary rat HSCs. NAFLD leads to cell type-specific rearrangements in retinol metabolism leading to vitamin A accumulation in hepatocytes. This may promote disease progression and/or affect therapeutic approaches targeting nuclear receptors.

Methicillin-resistant Staphylococcus aureus (MRSA) is a clinically prevalent bacterium and is resistant to many drugs. Genetic factors such as mec genes are considered to be responsible for this resistance. Recently, Staphylococcal Cassette Chromosome mec (SCCmec) element mutations produced mecC, a new genetic variant that encodes a transpeptidase enzyme (63% similarity with mecA-encoded PBP2a). This cross-sectional study was conducted to establish the prevalence of the mecA and mecC genes among phenotypically identified MRSA and their effectiveness against different antibiotics in clinical specimens. The prevalence of Staphylococcus aureus was 10.2% (n = 102) in the total number of clinical specimens collected (n = 1000). However, the prevalence of MRSA was 6.3% (n = 63) of the total samples collected, while it was 61.8% among total Staphylococcus aureus isolates. mec genes were confirmed in 96.8% (n = 61) isolates of MRSA, while 3.2% (n = 2) were found to be negative for mec genes. The combination of mecA and mecC was detected in 57.1% (n = 36) of the MRSA isolates. The prevalence of lone mecA was 31.8% (n = 20) and that of lone mecC was 7.9% (n = 5) among all the MRSA samples. Penicillin and amoxicillin/clavulanic acid were the most resistant antibiotics followed by norfloxacin (91.2%), levofloxacin (87.1%), ciprofloxacin (83.9%), azithromycin (78.6%), erythromycin (77.4%), moxifloxacin (69.8%), and sulfamethoxazole/trimethoprim (54.9%). On the other hand, vancomycin and teicoplanin (98.4%) were more effective drugs against MRSA followed by linezolid (96.7%), clindamycin (84.6%), chloramphenicol (83.7%), fusidic acid (70.6%), gentamicin (67.7%), and tetracycline (56.8%). In conclusion, a significant prevalence of mecA and mecC has been found among MRSA isolated from clinical specimens, which is likely responsible for antibiotic resistance in MRSA in our clinical settings. However, vancomycin, teicoplanin, and linezolid were found the top three most effective drugs against MRSA in our clinical settings. Thus, MRSA endemics in local areas require routine molecular and epidemiological investigation.

Peste des Petits Ruminants (PPR) is an important viral disease of small ruminants and is endemic in Pakistan. In the following study, samples from two outbreaks of PPR in goats have been subjected to laboratory investigations. The Peste des Petits Ruminants virus (PPRV) genome was detected using both conventional and real‐time PCR. Genetic characterization of the local PPRV field isolates was conducted by sequencing 322 bp of the fusion (F) gene and 255 bp of the nucleoprotein (N) gene. The phylogenetic tree based on the F gene clustered samples from both outbreaks into lineage 4 along with other Asian isolates, specifically into subcluster 1 along with isolates from Middle East. Analysis of N gene revealed a different pattern. In this case, the Pakistani samples clustered with Chinese, Tajikistani and Iranian isolates, which probably represents the true geographical pattern of virus circulation. This is the first report presenting the phylogenetic tree based on N gene as well as performing a parallel comparison of the trees of F and N gene together from Pakistani isolates. The results of this study shed light on the PPRV population in Pakistan and emphasize the importance of using molecular methods to understand the epidemiology. Such understanding is essential in any efforts to control the number and impact of outbreaks that are occurring in endemic countries such as Pakistan, especially in the current scenario where OIE and FAO are eager to control and subsequently eradicate PPR from the globe, as has been achieved for Rinderpest.

To determine the presence of Babesia bovis (B. bovis) in large ruminants in southern Punjab and its effect on hematological and serum biochemical profile of host animals. Blood samples were collected from 144 large ruminants, including 105 cattle and 39 buffaloes, from six districts in southern Punjab including Multan, Layyah, Muzaffar Garh, Bhakar, Bahawalnagar and Vehari. Data on the characteristics of animals and herds were collected through questionnaires. Different blood (hemoglobin, glucose) and serum (ALT, AST, LDH, cholesterol) parameters of calves and cattle were measured and compared between parasite positive and negative samples to demonstrate the effect of B. bovis on the blood and serological profile of infected animals. 27 out of 144 animals, from 5 out of 6 sampling districts, produced the 541-bp fragment specific for B. bovis. Age of animals (P=0.02), presence of ticks on animals (P=0.04) and presence of ticks on dogs associated with herds (P=0.5) were among the major risk factors involved in the spread of bovine babesiosis in the study area. ALT concentrations were the only serum biochemical values that significantly varied between parasite positive and negative cattle. : This study has reported for the first time the presence of B. bovis in large ruminant and the results can lead to the prevention of babesiosis in the region to increase the livestock output.