Pancreatic ductal adenocarcinoma (PDAC) is among the cancers with the poorest prognoses due to its highly malignant features. BTB and CNC homology 1 (BACH1) has been implicated in RAS-driven tumor formation. We focused on the role of BACH1 in PDAC, more than 90% of which have KRAS mutation. Knockdown of BACH1 in PDAC cell lines reduced cell migration and invasion, in part, by increasing E-cadherin expression, whereas its overexpression showed opposite effects. BACH1 directly repressed the expression of FOXA1 that is known to activate the expression of CDH1 encoding E-cadherin and to inhibit epithelial-to-mesenchymal transition. BACH1 also directly repressed the expression of genes important for epithelial cell adhesion including CLDN3 and CLDN4. In a mouse orthotopic implantation model, BACH1 was required for the high metastatic ability of AsPC-1 cells. IHC analysis of clinical specimens with a newly developed anti-BACH1 mAb revealed that high expression of BACH1 is a poor prognostic factor. These results suggest that the gene regulatory network of BACH1 and downstream genes including CDH1 contribute to the malignant features of PDAC by regulating epithelial-tomesenchymal transition.Significance: Greater understanding of the gene regulatory network involved in epithelial-to-mesenchymal transition of pancreatic cancer cells will provide novel therapeutic targets and diagnostic markers.

Nutritional steatohepatitis is closely associated with dysregulation of lipid metabolism and oxidative stress control. ADH3 is a highly conserved bifunctional enzyme involved in formaldehyde detoxification and termination of nitric oxide signaling. Formaldehyde and nitric oxide are nonenzymatically conjugated with glutathione, which is regenerated after ADH3 metabolizes the conjugates. To clarify roles of ADH3 in nutritional liver diseases, we placed Adh3-null mice on a methionine- and choline-deficient (MCD) diet. The Adh3-null mice developed steatohepatitis more rapidly than wild-type mice, indicating that ADH3 protects liver from nutritional steatohepatitis. NRF2, which is a key regulator of cytoprotective genes against oxidative stress, was activated in the Adh3-null mice with liver damage. In the absence of NRF2, the Adh3 disruption caused severe steatohepatitis by the MCD diet feeding accompanied by significant decrease in glutathione, suggesting cooperative function between ADH3 and NRF2 in the maintenance of cellular glutathione level for cytoprotection. Conversely, with enhanced NRF2 activity, the Adh3 disruption did not cause steatohepatitis but induced steatosis, suggesting that perturbation of lipid metabolism in ADH3-deficiency is not compensated by NRF2. Thus, ADH3 protects liver from steatosis by supporting normal lipid metabolism and prevents progression of steatosis into steatohepatitis by maintaining the cellular glutathione level.

Materials and Methods: A total of 609 clinical cases were considered during the study period and the diagnosis of the cases was performed based on detailed history, clinical signs, and clinical examinations including color, odor and consistency of rumen fluid and rumen microflora movements. The confirmations of the cases were done by measuring the pH of the rumen fluid and the blood. Calcium level of blood was measured by biochemical analyzer to determine hypocalcaemia. Results:The overall prevalence of ruminal acidosis in ruminants were 2.6% and found no significant differences (p>0.05) between cattle (4.04%) and goat (1.9%). Moreover, there were no significant variation (p>0.05) was observed among the sex (male and female of cattle and goats were 5.1% & 3.4% and 3.3% & 2.1%, respectively), breeds (non-descriptive and descriptive breeds of cattle and Black Bengal and Jamnapari goats were 3.7% & 4.7% and 1.8% & 2.1%, respectively) and two age groups of cattle and goats (3.7% & 4.3% and 2.02% &1.8%, respectively). Among the risk factors of ruminal acidosis feeding of cooked rice was highest (50% and 62.5% in cattle and goats, respectively) followed by feeding of rice gruel (25%) and feeding jackfruit residue, potato, bread each by 12.5%. A positive correlation was observed between duration of illness Conclusion: Ruminal acidosis is a vital nutritional problem in ruminants in terms of substantial health problem and economic point of views. This study recommends that farmers should abstain from feeding of the large amount of easily digestible carbohydrates to ruminants at a time.

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The crossbred dairy cattle (CDC) have been gaining popularity in the tropical countries for their increased milk yield within a short period of time because of heterogenic additive gene action. Hence, we aimed to investigate whether genotype, parity, season and their interactions had any effect on average daily milk yield (ADMY) of the CDC in a dairy farm at Chattogram district, Bangladesh, for a period of 3 years from January 2016 to December 2019. Total 16,425 retrospective lactation records of 150 multiparous Sahiwal × Friesian1 (Sahiwal = 50%, HF = 50%), Local × Friesian1 (Local = 50%, HF = 50%) and Local × Friesian2 (Local = 25%, HF = 75%) CDC from the first to the third parities (50 for each parity) were collected from the farm records. The generalized linear model and principal component analysis identified substantial impacts of genotype, parity, season and their interactions on ADMY of the CDC. The herd level least squared ADMY was 11.22 ± 0.04 kg/days on a 305‐days typical lactation period. The Sahiwal × Friesian1 CDC produced 7.2% and 5.5% more milk than the Local × Friesian1 and Local × Friesian2 respectively. The CDC produced maximum milk in the second parity, which was 7.8% and 0.34% more than the first and third parities. Similarly, the highest ADMY was recorded in the spring, which was 10.8%, 7.3% and 6.6% more than the fall, summer and winter respectively. It was concluded that the Sahiwal × Friesian1 crossbred produced maximum milk in the spring season at the second parity while other determinants remained constant. The changing patterns of milk yield in different genotype, parity and seasons provided scientific evidence for improving feeding strategy to optimize herd level milk yield of CDC in the commercial dairy farms under tropical perspective.