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Discovered in 1996, PCSK7 is the seventh of the nine-membered proprotein convertase subtilisin-kexin (PCSK) family. This article reviews the various aspects of the multifaceted biology of PCSK7 and what makes it an exciting new target for metabolic dysfunction-associated steatotic liver disease (MASLD) affecting ∼30% of the population globally, dyslipidemia, cardiovascular disease (CVD), and likely cancer/metastasis. We will systematically review and discuss all the available epidemiological data, structural, cell biology, and in vivo evidence that eventually led to the discovery of PCSK7 as a novel post-translational regulator of apolipoprotein B. Interestingly, PCSK7 is the only convertase, other than PCSK9, that exhibits non-canonical/non-enzymatic functions, which will be amply described in this review. The data so far suggested that PCSK7 is a potential safe target in MASLD treatment. This was based on human epidemiological data, as well as mouse Pcsk7 knockout and mRNA translation inhibition using hepatocyte-targeted antisense oligonucleotides following a diet-induced MASLD. Additionally, of all the 9 convertases only the gene deletion of Pcsk7 and/or Pcsk9 in mice leads to healthy and fertile animals with no apparent deleterious consequences, suggesting that their pharmacological targeting is likely safe. Accordingly, the synergistic effects of inhibiting both PCSK7 and PCSK9 in a clinical setting may represent a novel therapy for various diseases. We believe that the current surge in oligonucleotide therapy, with many FDA-approved oligonucleotide-based drugs now available in the clinics, and the urgent need for novel MASLD therapeutics present an opportune moment for this timely review article., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Aim: Telemedicine has emerged as a potential solution to enhance postoperative follow-up care after dental implant surgery, offering the convenience of remote monitoring and reduced need for in-person visits., Materials and Methods: Participants were randomly assigned to either the telemedicine group (n = 15) or the in-person group (n = 15). In the telemedicine group, patients received remote follow-up care through virtual consultations, during which they could communicate their concerns and share images of the surgical site. The in-person group received standard in-person follow-up visits. Patient satisfaction was measured using a standardized survey, with responses collected on a Likert scale., Results: Telemedicine group exhibited comparable levels of patient satisfaction (mean satisfaction score ± standard deviation: 4.6 ± 0.3) to the in-person group (4.7 ± 0.2). Moreover, clinical outcomes, including wound healing assessment, were similar between the two groups. No significant differences were observed in the incidence of postoperative complications or the need for additional interventions., Conclusion: In conclusion, this pilot study demonstrates that telemedicine is an effective alternative to traditional in-person follow-up care for postoperative dental implant surgery patients. It offers comparable patient satisfaction and clinical outcomes while proving to be more cost-effective., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Background: Epidemiological evidence links the proprotein convertase subtilisin/kexin 7 (PCSK7) to triglyceride (TG) metabolism. We associated the known PCSK7 gain-of-function non-coding SNP rs236918 with higher levels of plasma apolipoprotein B (apoB) and the loss-of-function coding variant p.Pro777Leu (SNP rs201598301) with lower apoB and TG. Herein, we aimed to unravel the in vivo role of liver PCSK7., Methods: We biochemically defined the functional role of PCSK7 in lipid metabolism using hepatic cell lines and Pcsk7 -/- mice. Our findings were validated following subcutaneous administration of hepatocyte-targeted N-acetylgalactosamine (GalNAc)-antisense oligonucleotides (ASOs) against Pcsk7., Results: Independent of its proteolytic activity, membrane-bound PCSK7 binds apoB100 in the endoplasmic reticulum and enhances its secretion. Mechanistically, the loss of PCSK7/Pcsk7 leads to apoB100 degradation, triggering an unfolded protein response, autophagy, and β-oxidation, eventually reducing lipid accumulation in hepatocytes. Non-alcoholic fatty liver disease (NAFLD) was induced by a 12-week high fat/fructose/cholesterol diet in wild type (WT) and Pcsk7 -/- mice that were then allowed to recover on a 4-week control diet. Pcsk7 -/- mice recovered more effectively than WT mice from all NAFLD-related liver phenotypes. Finally, subcutaneous administration of GalNAc-ASOs targeting hepatic Pcsk7 to WT mice validated the above results., Conclusions: Our data reveal hepatic PCSK7 as one of the major regulators of apoB, and its absence reduces apoB secretion from hepatocytes favoring its ubiquitination and degradation by the proteasome. This results in a cascade of events, eventually reducing hepatic lipid accumulation, thus supporting the notion of silencing PCSK7 mRNA in hepatocytes for targeting NAFLD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nabil G Seidah has patent METHOD FOR REDUCING HEPATIC TRIGLYCERIDES pending to Nabil G Seidah., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study is a comparative analysis of the biochemical, hormonal, and mineral compositions of follicular fluid in preovulatory and cystic follicles of water buffalo ( Bubalus bubalis ). In total, reproductive tracts from 215 buffalo along with intact ovaries were collected randomly from an abattoir. The incidence of cystic conditions found in this study was 3.72% (8/215), involving the right ovary in 62.5% of instances and the left ovary in 37.5% of instances during the non-breeding season. Follicular fluid was aspirated from preovulatory follicles (12-15 mm diameter, oestrogen-active, follicular phase or stage IV corpus luteum on one of the two ovaries, n = 10) and cystic follicles (at least 20 mm diameter, no corpus luteum on any one of the two ovaries, n = 8). The follicular fluid samples were assayed for biochemical components (uric acid, creatinine, blood urea nitrogen, cholesterol, total protein, glucose, ascorbic acid, and alkaline phosphatase), hormones (progesterone, estradiol, and insulin), and minerals (calcium, magnesium, phosphorus, copper, zinc, and cobalt). Cystic follicles had greater ( P < 0.05) concentrations of creatinine, blood urea nitrogen, cholesterol, progesterone, copper, zinc, and cobalt, and lesser ( P < 0.05) concentrations of uric acid, glucose, ascorbic acid, estradiol, insulin, calcium, magnesium, and phosphorus compared with preovulatory follicles. These results indicated the marked differences in follicular fluid composition between preovulatory and cystic follicles in buffalo. Some of the changes were indicative of oxidative stress and disturbed steroidogenesis, two important mechanisms shown to be associated with cystic ovarian disease in various species. Further studies are warranted to investigate whether these differences are directly or indirectly involved in the formation of cystic follicles or are mere manifestations of the condition.

In the study, melatonin, a known antioxidant pineal peptide was used as an additive in the tris-egg yolk glycerol-based semen extender in Hariana bull semen and post-thaw sperm characters were evaluated. In the study, Group I was a control without melatonin; and Group II, III, and IV were having 0.5 mM, 1 mM, and 2 mM melatonin/80 × 10 6 spermatozoa, respectively were treatment groups. Thirty-two semen ejaculates from 4 Hariana bulls were processed for freezing and post-thaw sperm characteristics were evaluated. Sperm motility, velocity, the viability with intact membrane, and total antioxidant capacity were markedly (P < 0.05) improved in Group IV compared to all other groups. The lipid peroxidation and total protein carbonylation were substantially (P < 0.05) decreased in Group IV compared to all other groups. The population of cryocapacitated, acrosome-reacted, and apoptotic-like spermatozoa were significantly (P < 0.05) decreased in Group IV. Further, the relative band intensity of 74 kDa protein and percent of spermatozoa showing positive immune reactivity to tyrosine-phosphorylated proteins was decreased in Group IV. The progesterone-receptor ligand binding, in vitro capacitation response, and Vanguard distance were markedly (P < 0.05) improved in Group IV. In summary- Group IV having 2 mM melatonin was found to be optimal in providing cryoprotective effects to Hariana bull spermatozoa after freezing-thawing and can be suitably used as a semen additive during semen cryopreservation., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest with any other people or organizations in any financial or personal relationship., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this study, the cryoprotective potential of natural antioxidant curcumin in Hariana bull semen was evaluated as an additive in a tris-based extender with the assessment of motility and motion parameters of spermatozoa, membrane intactness, progesterone-receptor binding, protein carbonyl content, cervical mucus penetration, cryocapacitation-associated and apoptotic-like changes. The collected ejaculates were divided into five groups in the tris-based extender (control without curcumin-I, 10 µM-II, 25 µM-III, 50 µM-IV and 75µM-V) and were cryopreserved. Groups II and III containing 10 and 25 µM curcumin substantially (p < .05) improved the post-thaw sperm parameters like viability, motility, and velocity parameters; intact acrosome and membrane; lowered protein carbonyl content; DNA fragmentation and cryocapacitation-associated changes in comparison to control. It was interesting to note that early apoptotic-like changes in sperm cells were significantly (p < .05) decreased in Group II along with an increase in a higher population of sperm cells having high mitochondrial transmembrane potential. Higher progesterone-receptor binding, Vanguard distance and in vitro capacitation response were observed only in Group II (10µM) compared to other groups. In conclusion, curcumin in a semen extender manifests cryoprotective effects and may be incorporated at 10 µM concentration in a Hariana bull semen extender for better post-thaw sperm quality., (© 2021 Wiley-VCH GmbH.)