The Synergistic Roles of Cholecystokinin B and Dopamine D5 Receptors on the Regulation of Renal Sodium Excretion.

Renal dopamine D1-like receptors (D1R and D5R) and the gastrin receptor (CCKBR) are involved in the maintenance of sodium homeostasis. The D1R has been found to interact synergistically with CCKBR in renal proximal tubule (RPT) cells to promote natriuresis and diuresis. D5R, which has a higher affinity for dopamine than D1R, has some constitutive activity. Hence, we sought to investigate the interaction between D5R and CCKBR in the regulation of renal sodium excretion. In present study, we found D5R and CCKBR increase each other\u27s expression in a concentration- and time-dependent manner in the HK-2 cell, the specificity of which was verified in HEK293 cells heterologously expressing both human D5R and CCKBR and in RPT cells from a male normotensive human. The specificity of D5R in the D5R and CCKBR interaction was verified further using a selective D5R antagonist, LE-PM436. Also, D5R and CCKBR colocalize and co-immunoprecipitate in BALB/c mouse RPTs and human RPT cells. CCKBR protein expression in plasma membrane-enriched fractions of renal cortex (PMFs) is greater in D5R-/- mice than D5R+/+ littermates and D5R protein expression in PMFs is also greater in CCKBR-/- mice than CCKBR+/+ littermates. High salt diet, relative to normal salt diet, increased the expression of CCKBR and D5R proteins in PMFs. Disruption of CCKBR in mice caused hypertension and decreased sodium excretion. The natriuresis in salt-loaded BALB/c mice was decreased by YF476, a CCKBR antagonist and Sch23390, a D1R/D5R antagonist. Furthermore, the natriuresis caused by gastrin was blocked by Sch23390 while the natriuresis caused by fenoldopam, a D1R/D5R agonist, was blocked by YF476. Taken together, our findings indicate that CCKBR and D5R synergistically interact in the kidney, which may contribute to the maintenance of normal sodium balance following an increase in sodium intake

Association between sarcopenia and prognosis of hepatocellular carcinoma: A systematic review and meta-analysis

BackgroundSarcopenia, characterized by the loss of muscle mass, strength, and physical ability, occurs with aging and certain chronic illnesses such as chronic liver diseases and cancer. Sarcopenia is common in liver cirrhosis and hepatocellular carcinoma (HCC). Previous reports of association between sarcopenia and prognosis of HCC have been inconsistent. Therefore, the present systematic review and meta-analysis aimed to investigate the impact of sarcopenia on the survival of patients with HCC.MethodsA systematic literature search was conducted using PubMed, EMBASE, and Web of Science electronic databases from inception to May 1, 2022. We included retrospective or prospective studies investigating the association between sarcopenia and overall survival (OS) and/or progression free survival (PFS) of HCC. We applied the Quality in Prognosis Studies (QUIPS) instrument to evaluate the risk of bias and quality of included studies. The primary and secondary outcomes were the associations of sarcopenia with OS and PFS, respectively, expressed by a pooled hazard ratio (HR) and corresponding 95% confidence interval (CI). Subgroup analysis and sensitivity analysis were performed. We further evaluated the publication bias by the funnel plot and Begg’s test.ResultsA total of 42 studies comprising 8,445 patients were included. The majority of included studies were at an overall low risk of bias. The pooled prevalence of sarcopenia was 39% (95% CI: 33–45%) (n = 8,203). Sarcopenia was associated with an increased risk of shorter OS, with a pooled adjusted HR of 1.84 (95% CI: 1.62–2.09). An independent association between sarcopenia and reduced PFS was observed (HR = 1.33, 95% CI: 1.12–1.56).ConclusionThe prevalence of sarcopenia was approximately 39% among patients with HCC. Sarcopenia was independently associated with reduced OS and PFS in HCC irrespective of treatment modalities. It is imperative that interventions aimed at alleviating sarcopenia and restoring muscle mass be implemented in order to improve the survival of patients with HCC.Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022337797], identifier [CRD42022337797]

The Effects of ATIR Blocker on the Severity of COVID-19 in Hypertensive Inpatients and Virulence of SARS-CoV-2 in Hypertensive hACE2 Transgenic Mice.

Angiotensin-converting enzyme 2 (ACE2) is required for the cellular entry of the severe acute respiratory syndrome coronavirus 2. ACE2, via the Ang-(1-7)-Mas-R axis, is part of the antihypertensive and cardioprotective effects of the renin-angiotensin system. We studied hospitalized COVID-19 patients with hypertension and hypertensive human(h) ACE2 transgenic mice to determine the outcome of COVID-19 with or without AT1 receptor (AT1R) blocker treatment. The severity of the illness and the levels of serum cardiac biomarkers (CK, CK-BM, cTnI), as well as the inflammation markers (IL-1, IL-6, CRP), were lesser in hypertensive COVID-19 patients treated with AT1R blockers than those treated with other antihypertensive drugs. Hypertensive hACE2 transgenic mice, pretreated with AT1R blocker, had increased ACE2 expression and SARS-CoV-2 in the kidney and heart, 1 day post-infection. We conclude that those hypertensive patients treated with AT1R blocker may be at higher risk for SARS-CoV-2 infection. However, AT1R blockers had no effect on the severity of the illness but instead may have protected COVID-19 patients from heart injury, via the ACE2-angiotensin1-7-Mas receptor axis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12265-021-10147-3