BACKGROUND:Our previous studies have shown that the poly(hydroxybutyrate- co-hydroxyvalerate) - sol-gel bioactive glass (PHBV-SGBG) has good biocompatibility and promote bone tissue repair, but its specific role in periodontal tissue regeneration has not been investigated. OBJECTIVE:To investigate the periodontal regenerative effects of a PHBV-SGBG scaffold in beagle dogs. METHODS:Alveolar bone defects (5 mm×5 mm) were surgicaly created bilateraly at the buccal side of the mandibular third and fourth premolars of four beagle dogs. PHBV-SGBG scaffold was randomly filed in the defects as experimental group and nothing was put into the contralateral as control group. Histological and scanning electron microscopy observations, cone-beam CT evaluation and the Ca/P concentration ratio analysis were processed at 2, 4, 8 and 12 weeks after surgery. RESULTS AND CONCLUSION:After surgery, the height of the regenerated tissue increased with time in both groups, and the regenerated tissue height in the experiment group was higher than that in the control group (P < 0.05). At 12 weeks after surgery, the Ca/P concentration ratio of the experiment group was close to that in the normal tissue (P > 0.05), but higher than that of the control group (P < 0.05); the histological observation showed that the regenerated tissue of the experimental group was close to the normal tissue, and the regenerated tissue of the control group tended to be mature, with a smal amount of new blood vessels. Under the scanning electron microscope, no scaffold structure was visible in the experimental group with the presence of bone lacuna at 8 weeks after surgery, while in the control group, there was no bone lacuna and obvious osteoblasts; at 12 weeks after surgery, the structure of the regenerated tissue of experimental group was more regular and close to the normal tissue with no remarkable osteoblasts, and in the control group, the regenerated tissue was disordered, with several cavity. These results show that the PHBV-SGBG scaffold can enhance periodontal bone regeneration effectively.

Adolescent ; Adult ; Aged ; Child ; Female ; Follow-Up Studies ; Gastrointestinal Hemorrhage ; complications ; surgery ; Humans ; Hypertension, Portal ; mortality ; surgery ; Male ; Middle Aged ; Renal Veins ; surgery ; Splenic Vein ; surgery ; Time Factors

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment