Mapping the effect of drugs on ACE2 as a novel target site for COVID-19 therapy.

Angiotensin converting enzyme 2 (ACE2) has potentially conflicting roles in health and disease. COVID-19 coronavirus binds to human cells via ACE2 receptor, which is expressed on almost all body organs. Boosting the ACE2 receptor levels on heart and lung cells may provide more cellular enter to virus thereby worsening the infection. Therefore, among the drug targets, ACE2 is suggested as a vital target of COVID-19 therapy. This hypothesis is based on the protective role of the drugs acting on ACE2. Therefore, this review discusses the impact and challenges of using ACE2 as a target in the current therapy of COVID-19.

Vitamin D status in children and adolescents with autoimmune thyroiditis.

BACKGROUND: Vitamin D deficiency is a global health problem. Its role as an immune modulator has been recently emphasized. There is increasing evidence for the significant role of vitamin D in reducing the incidence of autoimmune diseases. However, little is known about the status of vitamin D in children and adolescents with autoimmune thyroiditis (AIT). OBJECTIVE: The goal of the present study was to assess vitamin D status in Egyptian children and adolescents with AIT and to explore its relation to biomarkers of autoimmunity and thyroid function. DESIGN: A prevalence case-control study that included 56 children with AIT and 56 healthy, age- and sex-matched subjects that served as the control group. The following was done for all participants: thorough history, physical examination, thyroid ultrasound, measurement of thyroid-stimulating hormone (TSH), free thyroxin (FT4), anti-thyroid peroxidase antibodies (TPOAb), anti-thyroglobulin antibody (TgAb) and assessment of serum 25-hydroxy vitamin D (25OHD) level. RESULTS: Overt hypothyroidism was detected in 42/56 while subclinical hypothyroidism was detected in 14/56 of the studied patients. Vitamin D deficiency rate was significantly higher in the AIT group compared to the control subjects (71.4 vs 21.4 %, P < 0.001). In AIT group, the mean level of 25OHD was significantly lower compared to the control group (16.2 ± 8.2 vs 33.9 ± 12.7 nmol/L, P < 0.001). The difference was more evident in patients with overt hypothyroidism than those with subclinical hypothyroidism (P < 0.01). There were significant negative correlations between serum 25OHD and age, duration of the disease, BMI, anti-TPOAb, anti-TGAb and TSH (P < 0.001 each). On the other hand, serum 25OHD correlated positively with FT4 levels. While 25OHD level was an independent risk factor for AIT, it failed to qualify as an independent risk for the progression of AIT to overt hypothyroidism after adjustment for other potential confounding factors; age, sex and BMI. CONCLUSIONS: Low serum vitamin D is significantly associated with AIT in Egyptian children. However, vitamin D level is not an independent risk for the progression of AIT to overt hypothyroidism. BMI may have an influence on serum 25OHD levels.

MUC4 regulates cellular senescence in head and neck squamous cell carcinoma through p16/Rb pathway.

The limited effectiveness of therapy for patients with advanced stage head and neck squamous cell carcinoma (HNSCC) or recurrent disease is a reflection of an incomplete understanding of the molecular basis of HNSCC pathogenesis. MUC4, a high molecular weight glycoprotein, is differentially overexpressed in many human cancers and implicated in cancer progression and resistance to several chemotherapies. However, its clinical relevance and the molecular mechanisms through which it mediates HNSCC progression are not well understood. This study revealed a significant upregulation of MUC4 in 78% (68/87) of HNSCC tissues compared with 10% positivity (1/10) in benign samples (P=0.006, odds ratio (95% confidence interval)=10.74 (2.0-57.56). MUC4 knockdown (KD) in SCC1 and SCC10B HNSCC cell lines resulted in significant inhibition of growth in vitro and in vivo, increased senescence as indicated by an increase in the number of flat, enlarged and senescence-associated ß-galactosidase (SA-ß-Gal)-positive cells. Decreased cellular proliferation was associated with G0/G1 cell cycle arrest and decrease expression of cell cycle regulatory proteins like cyclin E, cyclin D1 and decrease in BrdU incorporation. Mechanistic studies revealed upregulation of p16, pRb dephosphorylation and its interaction with histone deacetylase 1/2. This resulted in decreased histone acetylation (H3K9) at cyclin E promoter leading to its downregulation. Orthotopic implantation of MUC4 KD SCC1 cells into the floor of the mouth in nude mice resulted in the formation of significantly smaller tumors (170±18.30 mg) compared to those (375±17.29 mg) formed by control cells (P=0.00007). In conclusion, our findings showed that MUC4 overexpression has a critical role by regulating proliferation and cellular senescence of HNSCC cells. Downregulation of MUC4 may be a promising therapeutic approach for treating HNSCC patients.

Amelioration with vessel dilator of acute tubular necrosis and renal failure established for 2 days.

Seventeen Sprague-Dawley rats had ischemic nonoliguric acute renal failure (ARF) induced by vascular clamping resulting in their preischemic blood urea nitrogen (BUN) and creatinine levels of 16 +/- 1 and 0.56 +/- 0.05 mg/dl to increase to 162 +/- 4 and 8.17 +/- 0.5 mg/dl, P < 0.001, respectively, at day 4 of postischemia. Vessel dilator, a 37-amino-acid cardiac peptide hormone (0.3 microg x kg(-1) x min(-1) ip), decreased the BUN and creatinine levels to 53 +/- 17 mg/dl and 0.98 +/- 0.12 mg/dl (P < 0.001) in another seven animals where ARF had been established for 2 days. Water excretion doubled with ARF and was further augmented by vessel dilator. Transthoracic echocardiography revealed left ventricular dilation as a probable cause of the increase in vessel dilator in the circulation with ARF, and vessel dilator infusion reversed this dilation. At day 6 of ARF, mortality decreased to 14% with vessel dilator from 88% without vessel dilator. Acute tubular necrosis was <5% in the vessel dilator-treated rats compared with 25% to >75% in the placebo-treated ARF animals. We conclude that vessel dilator improves acute tubular necrosis and renal function in established ARF.

Productive, physiological and biochemical changes in imported and locally born Friesian and Holstein lactating cows under hot summer conditions of Egypt.

Twenty each of healthy lactating Friesian and Holstein cows were studied. They were of similar age and body weight, nonpregnant in their third lactation and 80-100 days post partum. The investigation was carried out for 8 weeks on two farms at the same time during the hot summer season in Egypt. The first farm was in Demietta (North east of the Nile Delta, 31 degrees 40' N) on 20 Friesian cows and the second was in Fakous (East of the Nile Delta, 30 degrees 40' N) on 20 Holstein cows. On each of the two farms, 10 cows were newly imported and 10 were born in Egypt. The average daily milk yield and total milk production in the third lactation of the newly imported cows were significantly higher than those of the locally born cows for both Friesians and Holsteins. At the same time, the T4, T3, urea-N, haematological values and AST enzyme activity in the newly imported cows were significantly lower than those in the locally born ones in both breeds, while the locally born cows showed significantly lower values for rectal temperature and respiration rate, as well as for AST and Alk-P enzyme activities, than the newly imported cows of either breed. Holstein cows surpassed the Friesians in milk production, as well as thyroid hormone secretion and cholesterol, haemoglobin, packed cell volume and erythrocyte count values. The opposite was found for serum total protein, urea-N and creatinine concentrations, leukocyte count and AST, ALT and Alk-P enzyme activities.