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About half of all cancer patients show a syndrome of cachexia, characterized by anorexia and loss of adipose tissue and skeletal muscle mass. Cachexia can have a profound impact on quality of life, symptom burden, and a patient’s sense of dignity. It is a very serious complication, as weight loss during cancer treatment is associated with more chemotherapy-related side effects, fewer completed cycles of chemotherapy, and decreased survival rates. Numerous cytokines have been postulated to play a role in the etiology of cancer cachexia. Cytokines can elicit effects that mimic leptin signaling and suppress orexigenic ghrelin and neuropeptide Y (NPY) signaling, inducing sustained anorexia and cachexia not accompanied by the usual compensatory response. Furthermore, cytokines have been implicated in the induction of cancer-related muscle wasting. Cytokine-induced skeletal muscle wasting is probably a multifactorial process, which involves a protein synthesis inhibition, an increase in protein degradation, or a combination of both. The best treatment of the cachectic syndrome is a multifactorial approach. Many drugs including appetite stimulants, thalidomide, cytokine inhibitors, steroids, nonsteroidal anti-inflammatory drugs, branched-chain amino acids, eicosapentaenoic acid, and antiserotoninergic drugs have been proposed and used in clinical trials, while others are still under investigation using experimental animals. There is a growing awareness of the positive impact of supportive care measures and development of promising novel pharmaceutical agents for cachexia. While there has been great progress in understanding the underlying biological mechanisms of cachexia, health care providers must also recognize the psychosocial and biomedical impact cachexia can have.

Staphylococcus aureus is a major pathogen in humans and causes serious problems due to antibiotic resistance. We investigated the antimicrobial effect of glycyrrhetinic acid (GRA) and its derivatives against 50 clinical S. aureus strains, including 18 methicillin-resistant strains. The minimum inhibitory concentrations (MICs) of GRA, dipotassium glycyrrhizate, disodium succinoyl glycyrrhetinate (GR-SU), stearyl glycyrrhetinate and glycyrrhetinyl stearate were evaluated against various S. aureus strains. Additionally, we investigated the bactericidal effects of GRA and GR-SU against two specific S. aureus strains. DNA microarray analysis was also performed to clarify the mechanism underlying the antibacterial activity of GR-SU. We detected the antimicrobial activities of five agents against S. aureus strains. GRA and GR-SU showed strong antibacterial activities compared to the other three agents tested. At a higher concentration (above 2x MIC), GRA and GR-SU showed bactericidal activity, whereas at a concentration of 1x MIC, they showed a bacteriostatic effect. Additionally, GRA and GR-SU exhibited a synergistic effect with gentamicin. The expression of a large number of genes (including transporters) and metabolic factors (carbohydrates and amino acids) was altered by the addition of GR-SU, suggesting that the inhibition of these metabolic processes may influence the degree of the requirement for carbohydrates or amino acids. In fact, the requirement for carbohydrates or amino acids was increased in the presence of either GRA or GR-SU. GRA and GR-SU exhibited strong antibacterial activity against several S. aureus strains, including MRSA. This activity may be partly due to the inhibition of several pathways involved in carbohydrate and amino acid metabolism.

Staphylococcus epidermidis is a commensal bacterium in humans. To persist in the bacterial flora of the host, some bacteria produce antibacterial factors such as the antimicrobial peptides known as bacteriocins. In this study, we tried to isolate bacteriocin-producing S . epidermidis strains. Among 150 S . epidermidis isolates from the oral cavities of 287 volunteers, we detected two bacteriocin-producing strains, KSE56 and KSE650. Complete genome sequences of the two strains confirmed that they carried the epidermin-harboring plasmid pEpi56 and the nukacin IVK45-like-harboring plasmid pNuk650. The amino acid sequence of epidermin from KSE56 was identical to the previously reported sequence, but the epidermin synthesis-related genes were partially different. The prepeptide amino acid sequences of nukacin KSE650 and nukacin IVK45 showed one mismatch, but both mature peptides were entirely similar. pNuk650 was larger and had an additional seven ORFs compared to pIVK45. We then investigated the antibacterial activity of the two strains against several skin and oral bacteria and found their different activity patterns. In conclusion, we report the complete sequences of 2 plasmids coding for bacteriocins from S . epidermidis , which were partially different from those previously reported. Furthermore, this is the first report to show the complete sequence of an epidermin-carrying plasmid, pEpi56.

Octacalcium phosphate and its collagen composite have been recognized as bone substitute materials possessing osteoconductivity and biodegradation properties. We evaluated the effectiveness of octacalcium phosphate and its collagen composite used for bone augmentation in major oral and maxillofacial surgeries in a clinical trial. Octacalcium phosphate and its collagen composite were used in cases of sinus floor elevation in 1- and 2-stage, socket preservation, cyst, and alveolar cleft procedures. A total of 60 patients were evaluated for effectiveness after the implantation of octacalcium phosphate and its collagen composite. Although sinus floor elevation in 1-stage, cyst, and alveolar cleft cases met the criteria for the judgment of success, sinus floor elevation in 2-stage and socket preservation groups did not meet the criteria in the initial evaluation. However, an additional evaluation for reconfirmation revealed the effectiveness of octacalcium phosphate and its collagen composite in those groups, and all evaluation results ultimately indicated the success of this clinical trial. Therefore, this clinical trial suggested that application of octacalcium phosphate and its collagen composite for oral and maxillofacial surgery was safe and effective and that octacalcium phosphate and its collagen composite could be a bone substitute candidate instead of autologous bone.

: Late-stage presentation of oral cancer remains a major challenge in low- and middle-income countries and contributes substantially to poor clinical outcomes. Data describing oral cancer presentation patterns in Indonesia remain limited. This study aimed to characterize the clinicopathological profile, stage distribution, treatment patterns, and exposure-related characteristics of oral cancer patients treated at a national referral center in Indonesia. : A retrospective study was conducted using medical records of 404 patients with histopathologically confirmed oral malignancies treated between 2021 and 2025. Descriptive analyses were performed to summarize demographic, clinicopathological, staging, treatment-related, and exposure-related characteristics. : The mean age at diagnosis was 49.17 ± 14.11 years, with a relatively balanced sex distribution. The tongue was the most common primary tumor site (76.0%), and oral squamous cell carcinoma (OSCC) represented the predominant histopathological diagnosis (81.9%). Late-stage presentation (stage III-IV) was observed in 64.1% of all cases and increased to 70.7% among patients with available staging information, while 29.2% of patients had incomplete or undefined staging data. Surgical treatment, either alone or combined with adjuvant therapies, was the most frequently employed treatment modality. Notably, 21.5% of patients had no documented definitive oncologic treatment during the recorded treatment period. Smoking was reported by 35.4% of patients, alcohol consumption by 4.0%, and a family history of cancer by 24.8%. : Advanced-stage oral cancer was highly prevalent in this referral-based cohort. The substantial burden of late-stage disease, together with incomplete staging information and the proportion of patients without documented definitive treatment, highlights challenges related to staging completeness, treatment documentation, and cancer care monitoring. These findings support efforts to strengthen early detection, referral coordination, and cancer care monitoring within the Indonesian healthcare system.

Staphylococcus aureus uses two-component systems (TCSs) to adapt to stressful environmental conditions. To colonize a host, S. aureus must resist bacteriocins produced by commensal bacteria. In a comprehensive analysis using individual TCS inactivation mutants, the inactivation of two TCSs, graRS and braRS, significantly increased the susceptibility to the class I bacteriocins, nukacin ISK-1 and nisin A, and inactivation of vraSR slightly increased the susceptibility to nukacin ISK-1. In addition, two ABC transporters (BraAB and VraDE) regulated by BraRS and one transporter (VraFG) regulated by GraRS were associated with resistance to nukacin ISK-1 and nisin A. We investigated the role of these three TCSs of S. aureus in co-culture with S. warneri, which produces nukacin ISK-1, and Lactococcus lactis, which produces nisin A. When co-cultured with S. warneri or L. lactis, the braRS mutant showed a significant decrease in its population compared with the wild-type, whereas the graRS and vraSR mutants showed slight decreases. Expression of vraDE was elevated significantly in S. aureus co-cultured with nisin A/nukacin ISK-1-producing strains. These results suggest that three distinct TCSs are involved in the resistance to nisin A and nukacin ISK-1. Additionally, braRS and its related transporters played a central role in S. aureus survival in co-culture with the strains producing nisin A and nukacin ISK-1.

Immune checkpoint inhibitors (ICIs) are used to treat several cancers, but they sometimes induce immune-related adverse events (irAEs). Patients with irAEs often have improved antitumor responses, but discontinuation of ICIs after irAEs is considered necessary. Resuming the use of ICIs after irAEs is preferable, but few studies have investigated the safety of ICI resumption after irAEs. Therefore, we evaluated the factors associated with the recurrence of irAEs after ICI resumption to investigate the safety of this approach. In this observational study, we enrolled patients treated with ICIs from September 2014 to March 2020 at our institution. Patient characteristics, ICIs, grades of irAEs, ICI discontinuation or resumption rates, and recurrence rates of irAEs after ICI therapy were analysed. Two-hundred eighty-seven patients were included in the present study, and 76 patients experienced grade 2 or higher irAEs. Forty-two patients underwent ICI resumption after recovering from irAEs, and 13 of them had a recurrence of irAEs. Among those 13 patients, six had a recurrence of the same irAE, and seven experienced other irAEs. Ten of the 13 patients had grade ≥2 irAEs, and none had fatal irAEs. In the grade 2 or higher irAE group, more patients had irAEs associated with multiple organs and of initial grade ≥2 than those in the grade 1 and no recurrent irAEs group. Patients with initial multisystemic irAEs and irAEs of grade ≥2 were more likely to experience relapse or develop new grade ≥2 irAEs after ICI resumption.

Accurate quantification of alveolar cleft defects for bone grafting remains difficult due to inconsistent anatomical boundaries. This study established an expert consensus on boundary landmarks for alveolar bone graft (ABG) planning and validated the accuracy and reliability of digital volumetric measurement methods. Three cleft specialists performed repeated simulated graft procedures in seven patient-specific 3D-printed models, first according to the operator's clinical judgment, and subsequently according to panel-derived consensus boundaries. Two radiologists independently conducted digital volumetric assessments in 3D X-ray imaging using four measurement approaches (axial tracing, interpolated axial tracing, landmark-based mirroring, and mesh-based mirroring), generating 56 independent digital segmentations to be evaluated against the consensus-based physical reference standard. Volumes of the defects were recorded, intra- and inter-rater reliabilities were calculated using the intraclass correlation coefficient (ICC), and differences among methods were analyzed. Operator-defined plans showed significant inter-operator differences ( < 0.001) with poor-to-excellent reliability (intra-rater ICC 0.060-0.967; inter-rater ICC 0.300-0.635). Consensus established standardized boundaries: tilted plane from base of anterior nasal spine to hard palate, cemento-enamel junctions, incisive canal, and alveolar contour. Consensus-based filling showed non-significant inter-rater differences ( = 0.139) and substantially improved reliability (intra-rater ICC 0.904-0.988; inter-rater ICC 0.622-0.861). Among the four digital methods evaluated, axial tracing demonstrated excellent reliability (intra-rater ICC 0.971-0.99; inter-rater ICC 0.965) and high accuracy (mean difference 0.001-0.026 cm ), with no significant difference ( = 0.999) from the physical reference standard. These proposed consensus-based boundary definitions and validated volumetric measurement methods improved the accuracy and reproducibility of personalized alveolar bone graft planning.

Helicobacter pylori ( Hp ) infection is related to the pathogenesis of chronic gastric disorders and extragastric diseases. Here, we examined the anorexigenic and anxiogenic effects of Hp vacuolating cytotoxin A (VacA) through activation of hypothalamic urocortin1 (Ucn1). VacA was detected in the hypothalamus after peripheral administration and increased Ucn1 mRNA expression and c-Fos-positive cells in the hypothalamus but not in the nucleus tractus solitarius. c-Fos and Ucn1-double positive cells were detected. CRF1 and CRF2 receptor antagonists suppressed VacA-induced anxiety and anorexia, respectively. VacA activated single paraventricular nucleus neurons and A7r5 cells; this activation was inhibited by phospholipase C (PLC) and protein kinase C (PKC) inhibitors. VacA causes anorexia and anxiety through the intracellular PLC-PKC pathway, migrates across the blood-brain barrier, and activates the Ucn1-CRF receptor axis.

Background: Better prognostic biomarkers for oral squamous cell carcinoma (OSCC) must be developed, particularly within the realm of clinically and frequently administered tests, to advise appropriate clinical therapy and follow-up. In this study, we retrospectively investigated which of the several inflammation-nutrition indicators might predict the prognosis of patients with OSCC. Methods:   The preoperative neutrophil-lymphocyte ratio (NLR), lymphocyte–monocyte ratio (LMR), platelet–lymphocyte ratio (PLR), CRP-albumin ratio (CAR), Glasgow prognostic score (GPS), modified GPS (mGPS), prognostic nutritional index (PNI), controlling nutrition status (CONUT), and modified CONUT (mCONUT) were retrospectively evaluated using blood samples collected 1–5 days before surgery. To estimate the effect on the prognosis of tumor progression, the mean values of the markers between stages I/II and III/IV were used for subgroup analysis. The multivariate Cox proportional hazards model included all independent variables significantly associated with survival in the univariate analysis to determine the independent variables. Results: A total of 112 patients (69 males and 43 females) with primary OSCC who underwent surgical treatment at our hospital were included. There were statistically significant differences in the mean values of monocytes, platelets, and albumin between stages I/II and III/IV. According to the multivariate Cox proportional hazards regression, a low PNI was associated with shorter overall survival (OS) and disease-free survival (DFS); women were associated with shorter DFS. Conclusion: The pretreatment PNI had excellent predictive value for the 5-year OS and DFS of patients with OSCC. Future large-scale prospective studies with a high sample size are needed to verify our findings in OSCC patients.