Combination of plant metabolites hinders starch digestion and glucose absorption while facilitating insulin sensitivity to diabetes.

Introduction: Diabetes mellitus (DM) is a common endocrine disease resulting from interactions between genetic and environmental factors. Type II DM (T2DM) accounts for approximately 90% of all DM cases. Current medicines used in the treatment of DM have some adverse or undesirable effects on patients, necessitating the use of alternative medications. Methods: To overcome the low bioavailability of plant metabolites, all entities were first screened through pharmacokinetic, network pharmacology, and molecular docking predictions. Experiments were further conducted on a combination of antidiabetic phytoactive molecules (rosmarinic acid, RA; luteolin, Lut; resveratrol, RS), along with in vitro evaluation (α-amylase inhibition assay) and diabetic mice tests (oral glucose tolerance test, OGTT; oral starch tolerance test, OSTT) for maximal responses to validate starch digestion and glucose absorption while facilitating insulin sensitivity. Results: The results revealed that the combination of metabolites achieved all required criteria, including ADMET, drug likeness, and Lipinski rule. To determine the mechanisms underlying diabetic hyperglycemia and T2DM treatments, network pharmacology was used for regulatory network, PPI network, GO, and KEGG enrichment analyses. Furthermore, the combined metabolites showed adequate in silico predictions (α-amylase, α-glucosidase, and pancreatic lipase for improving starch digestion; SGLT-2, AMPK, glucokinase, aldose reductase, acetylcholinesterase, and acetylcholine M2 receptor for mediating glucose absorption; GLP-1R, DPP-IV, and PPAR-γ for regulating insulin sensitivity), in vitro α-amylase inhibition, and in vivo efficacy (OSTT versus acarbose; OGTT versus metformin and insulin) as nutraceuticals against T2DM. Discussion: The results demonstrate that the combination of RA, Lut, and RS could be exploited for multitarget therapy as prospective antihyperglycemic phytopharmaceuticals that hinder starch digestion and glucose absorption while facilitating insulin sensitivity.

Clinicopathological analysis of 18 cases of secretory carcinoma of the salivary glands.

Background/purpose: Secretory carcinoma (SC) is a rare salivary gland tumor that featured by ETV6::NTRK3 gene fusion, and was included in the WHO Classification of Head and Neck Tumors since 2017. Nevertheless, the description of SCs by WHO is still vague. This study examined 18 SC cases by using both histomorphology and molecular pathology for diagnostic determination, especially immunohistochemical features of SCs. Materials and methods: Based on WHO characteristics, 18 patients with SC admitted between 2001 and 2022 were included in this study. Main histomorphological patterns, FISH analyses of the ETV6::NTRK3 gene fusion, and immunohistochemical analyses of S100, mammaglobin, DOG1, ADFP, CA6 and Ki-67 were performed. Results: Among the 18 SC patients, the median age of onset was 39.22 years. Grossly, the average tumor size in 2.96 cm with various texture from soft to tough. The majority patients were positive for S100, mammaglobin, and negative for DOG1, except for one patient negative for S100 (Case 18). All patients were positive for ADFP, and the majority patients were negative for CA6, except for Case 9. Two cases were found recurrence, and the tumor were found both in parotid gland with local invasion. Conclusion: Combined with the results of previous studies, we proposed that the combination of all five markers, S100, mammaglobin, DOG1, ADFP and CA6, could contribute more to differential diagnosis of SCs with other salivary carcinomas, especially with AciCC. The prognosis of SCs is optimistic in most cases, but larger patient cohort and long-term follow-up are still needed.

The effect of argon cold atmospheric plasma on the metabolism and demineralization of oral plaque biofilms.

Objective: The aim of this study was to design and optimize a cold atmospheric plasma (CAP) device that could be applied in an oral environment and to study its effects on plaque biofilm metabolism and regrowth, as well as microbial flora composition and enamel demineralization. Method: CAP was obtained through a dielectric barrier discharge device; the optical properties were analyzed using emission spectroscopy. The electrochemical analysis of plasma devices includes voltametric characteristic curves and Lissajous. The Streptococcus mutans (UA159) and saliva biofilms were treated in vitro, and the effects of CAP on biofilm metabolism were investigated using MTT and lactate dehydrogenase assays. The duration of antibacterial activity on biofilms was examined, scanning electron microscopy was used to observe the morphology of biofilms, and 16S rRNA sequencing was used to explore the influence of CAP on the microbial flora composition of saliva biofilms. An in vitro model of biofilm-enamel demineralization was designed, and the effect of CAP on enamel demineralization was evaluated by micro surface hardness and micro-CT analysis. Results: CAP had antibacterial proliferative ability toward Streptococcus mutans biofilms and saliva biofilms and was stronger than ultraviolet under the same tested conditions. After 24 h, the antibacterial effect disappeared, which proved the short-term timeliness of its bactericidal ability. CAP can inhibit the acid production of biofilms, and its inhibitory effect on saliva biofilms can be extended to 24 h. CAP had a strong ability to regulate the composition of plaque biofilms, especially for Lactococcus proliferation, a major acid-producing bacterium in microcosm biofilms. The CAP-treated enamels were more acid-tolerant than non-treated controls. Conclusion: CAP had an explicit bactericidal effect on caries-related biofilms, which is a short-term antibacterial effect. It can inhibit the acid production of biofilms and has a downregulation effect on Lactococcus in saliva biofilms. CAP can help reduce demineralization of enamel.

A DNA-Damage Inducible Gene Promotes the Formation of Antibiotic Persisters in Response to the Quorum Sensing Signaling Peptide in Streptococcus mutans.

Bacteria use quorum sensing (QS) to communicate with each other via secreted small autoinducers produced by individuals. QS allows bacteria to display a unified response that benefits the species during adaptation to environment, colonization, and defense against competitors. In oral streptococci, the CSP-ComDE QS is an inducible DNA damage repair system that is pivotal for bacterial survival. In the oral pathogen Streptococcus mutans, the QS system positively influences the formation of antibiotic persisters, cells that can survive antibiotic attack by entering a non-proliferative state. We recently identified a novel gene, pep299, that is activated in the persister cell fraction induced by QS. In this study, we focused our investigation on the role of pep299, a gene encoding a bacteriocin-like peptide, in the formation of antibiotic persisters. Mutant Δ299, unable to produce Pep299, showed a dramatic reduction in the number of stress-induced persisters. Using a co-culture assay, we showed that cells overproducing pep299 induced the formation of persisters in the mutant, suggesting that Pep299 was actively secreted and detected by neighboring cells. Cells exposed to DNA damage conditions activated the gene expression of pep299. Interestingly, our results suggested that the pep299 gene was also involved in the regulation of a QS-inducible toxin−antitoxin system. Our study suggests that the pep299 gene is at the core of the triggered persistence phenotype in S. mutans, allowing cells to transition into a state of reduced metabolic activity and antibiotic tolerance.

Warthin-like mucoepidermoid carcinoma and mucoepidermoid carcinoma, mucinous metaplasia involving Warthin tumor: three case reports.

Warthin-like mucoepidermoid carcinoma (MEC) is a recently identified MEC variant of the salivary gland. MEC morphologically mimics Warthin tumor (WT) but harbors the same chromosomal translocation t (11; 19) (q21; p13) as MEC. Thus, differential diagnosis is crucial. MEC involving WT is extremely rare in salivary glands. In this study, we reported a case of Warthin-like MEC, a case of MEC co-existing with WT, and a case of mucinous metaplasia in WT. We also discussed the possible link between WT and MEC.

Neonatal biliary atresia combined with preduodenal portal vein: A case report.

BACKGROUND: Congenital biliary atresia is a type of obstruction of the bile ducts inside and outside the liver, which can lead to cholestatic liver cirrhosis and eventually liver failure. The preduodenal portal vein (PD-PV) is a rare developmental malformation of the PV. The PV courses in front of the duodenum. However, very few cases of neonatal biliary atresia combined with PD-PV have been reported in the scientific literature. CASE SUMMARY: A 1-mo-and-4-d-old child was admitted to the hospital in January because of yellowish skin. After surgical consultation, surgical intervention was recommended. The child underwent Hilar-jejunal anastomosis, duodenal rhomboid anastomosis, and abdominal drainage under general anesthesia. During the operation, the PV was located at the anterior edge of the duodenum. CONCLUSION: Diagnoses: (1) Congenital biliary atresia; (2) PD-PV; and (3) Congenital cardiovascular malformations. Outcomes: Recommendation for liver transplantation. Lessons: The choice of treatment options for neonatal biliary atresia combined with PD-PV.

[Basaloid squamous cell carcinoma in gingiva: a case report].

As an aggressive subtype of squamous cell carcinoma, basaloid squamous cell carcinoma (BSCC) rarely occurs in the oral and maxillofacial region. The gingiva is an unusual site of BSCC. This study reported a 78-year-old male who presented with left maxillary pain. Clinical examination revealed a gingival mass in the left maxilla. Under microscope, the lesion showed typical comedo necrosis and peripheral palisading. Areas of glandular-like structures were also observed. Immunohistochemistry results revealed that the Ki-67 score of BSCC in this case was 28%, and S-100 was positive in some areas. However, P16 and CK7 were negative. Finally, a diagnosis of BSCC was made based on the pathological and immunohistochemical characteristics. The patient underwent subtotal maxillectomy. After 12 months later, the patient was alive with no evidence of disease. Combined with relevant literature, this article analyzed the clinicopathological features, differential diagnosis, diagnosis, treatment, and prognosis of BSCC. Although surgery remains the main treatment in the head and neck region, radiation-chemotherapy should be considered in some human papilloma virus-positive cases.