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Simple Summary: Oral cancer is a challenging disease to treat, and new therapies are needed to improve patient outcomes. Okanin, a natural compound derived from Bidens pilosa L., has been known for its anti-inflammatory properties, but its effects on cancer, particularly oral cancer, are less understood. In this study, we investigated the anticancer potential of okanin in human oral cancer cells. Our results showed that okanin effectively reduced the growth of oral cancer cells by inducing cell death through mechanisms involving both apoptosis and pyroptosis. Additionally, okanin inhibited tumor growth in a mouse model of oral cancer. These findings suggest that okanin may be a promising natural compound for developing new treatments for oral cancer. Background: Okanin, a flavonoid compound derived from Bidens pilosa L., has garnered attention for its anti-inflammatory properties. Although Bidens pilosa is commonly used in healthcare products and functional foods, the anticancer potential of okanin, particularly in oral cancer, remains underexplored. This study aims to investigate the effects of okanin on oral cancer cell lines and its potential as a therapeutic agent. Methods: The study involved assessing the cytotoxic effects of okanin on oral cancer cell lines SAS, SCC25, HSC3, and OEC-M1. The IC50 values were determined using methylene blue assays, and the clonogenic capacity was evaluated through colony formation assays. Flow cytometry was used to analyze cell cycle progression and apoptosis. Caspase-3/7 activity assays and annexin V/7-AAD staining confirmed the induction of apoptosis and pyroptosis. In vivo efficacy was assessed using a SAS xenograft model, and immunohistochemical analysis of xenograft tissue was performed to examine pyroptosis-related markers. Results: Okanin exhibited potent cytotoxic effects with IC50 values of 12.0 ± 0.8, 58.9 ± 18.7, 18.1 ± 5.3, and 43.2 ± 6.2 μM in SAS, SCC25, HSC3, and OEC-M1 cells, respectively. It caused dose- and time-dependent reductions in cell viability and significantly impaired clonogenic capacity. Flow cytometry revealed G2/M cell cycle arrest and increased sub-G1 population, indicating cell cycle disruption and death. Okanin induced both apoptosis and pyroptosis, as confirmed by caspase-3/7 activity and annexin V/7-AAD staining. In vivo, okanin reduced tumor growth and involved pyroptosis-related markers such as CASP1, GSDMC, GSDMD, and GSDME. Conclusions: Okanin demonstrates significant anticancer potential, particularly in oral cancer, by inducing both apoptosis and pyroptosis. Its efficacy in reducing tumor growth in vivo further supports its potential as a novel therapeutic option. Further mechanistic studies are needed to elucidate the pathways involved in okanin-mediated cell death and to explore its clinical applications. [ABSTRACT FROM AUTHOR]

Significant health risks are posed by meningitis due to its rapid progression, and challenges are encountered in intravenous antibiotic administration, especially in crossing the blood‐brain barrier. To address this, an inflammation‐activated, endogenous macrophage (MΦ)‐mediated oral prodrug delivery system is developed for targeted therapeutic interventions in bacterial meningitis treatment. This system is guided by inflammation‐derived chemoattractants and triggers drug release through inflammation‐induced reactive oxygen species (ROS). Comprised of naturally derived β‐glucans conjugated with the antibiotic cefotaxime (CTX) using a ROS‐responsive linker, nanoparticles (βGlus–CTX NPs) are formed in aqueous solutions. In a mouse model of Klebsiella pneumoniae‐induced meningitis, orally administered βGlus–CTX NPs are traversed by intestinal microfold cells, surpassing the intestine‐epithelial barrier, and are absorbed by resident endogenous MΦ. These MΦ‐mediated drug delivery vehicles are then traveled through the lymphatic and circulatory systems, crossing the compromised blood‐brain barrier, ultimately reaching inflamed brain tissues, guided by their derived chemoattractants. In ROS‐rich inflamed tissue environments, the linkers in the βGlus–CTX NPs are cleaved, releasing therapeutic CTX for localized treatment. Targeted antibiotic treatment for bacterial meningitis is offered by this oral, endogenous MΦ‐mediated prodrug delivery system, overcoming the robust gut‐to‐brain biological barriers and potentially enhancing effectiveness for comfortable home‐based treatment. [ABSTRACT FROM AUTHOR]

The dysregulated expression of cyclin genes can lead to the uncontrolled proliferation of cancer cells. Histone demethylase Jumonji-C domain-containing protein 5 (KDM8, JMJD5) and cyclin A1 (CCNA1) are pivotal in cell cycle progression. A promising candidate for augmenting cancer treatment is Allyl isothiocyanate (AITC), a natural dietary chemotherapeutic and epigenetic modulator. This study aimed to investigate AITC's impact on the KDM8/CCNA1 axis to elucidate its role in oral squamous cell carcinoma (OSCC) tumorigenesis. The expression of KDM8 and CCNA1 was assessed using a tissue microarray (TMA) immunohistochemistry (IHC) assay. In vitro experiments with OSCC cell lines and in vivo experiments with patient-derived tumor xenograft (PDTX) and SAS subcutaneous xenograft tumor models were conducted to explore AITC's effects on their expression and cell proliferation. The results showed elevated KDM8 and CCNA1 levels in the OSCC patient samples. AITC exhibited inhibitory effects on OSCC tumor growth in vitro and in vivo. Additionally, AITC downregulated KDM8 and CCNA1 expression while inducing histone H3K36me2 expression in oral cancer cells. These findings underscore AITC's remarkable anticancer properties against oral cancer, highlighting its potential as a therapeutic option for oral cancer treatment by disrupting the cell cycle by targeting the KDM8/CCNA1 axis. [ABSTRACT FROM AUTHOR]

This systematic review and meta‐analysis aimed to investigate the effect of nonalcoholic fatty liver disease (NAFLD) on bone mineral density (BMD) and the risk of osteoporosis and osteoporotic fracture in adults. We searched PubMed, MEDLINE, Embase, CINAHL, Web of Science, Cochrane Library, and Scopus for observational studies published from inception to January 2023 that reported adjusted effect sizes of NAFLD on BMD, osteopenia/osteoporosis, and osteoporotic fracture. The data were synthesized using multilevel and random‐effects models. A total of 19 studies were included; of these, nine (21,294 participants) evaluated the effect of NAFLD on BMD, six (133,319 participants) investigated the risk of osteoporosis, and five (227,901 participants) assessed the risk of osteoporotic fracture. This meta‐analysis showed that NAFLD was associated with decreased BMD (mean difference −0.019 g/cm2, 95% confidence interval [CI] −0.036 to −0.002, I2 = 93%) and increased risks of osteoporosis (adjusted risk ratio [RR] = 1.28, 95% CI 1.08 to 1.52, I2 = 84%) and osteoporotic fractures (adjusted RR = 1.17, 95% CI 1.00 to 1.37, I2 = 67%). Subgroup analyses revealed that NAFLD had a significantly detrimental effect on BMD in men and on the BMD of the femoral neck and total hip. Stratified analyses by ethnicity demonstrated that NAFLD was not associated with BMD, osteoporosis, or osteoporotic fracture in non‐Asian populations. The publication bias of all included studies was low; however, there was considerable heterogeneity among the studies, warranting a careful interpretation of the findings. Overall, our results suggest that NAFLD is associated with decreased BMD and an increased risk of osteoporosis or osteoporotic fractures. Male sex and the BMD of the femoral neck and total hip may be potential risk factors for decreased BMD in adults with NAFLD. Additionally, ethnic disparities were observed between Asian and non‐Asian populations regarding BMD and osteoporotic fractures. © 2023 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Background: The impact of associated chest wall injuries (CWI) on the complications of clavicle fracture repair is unclear to date. This study aimed to investigate the complications after surgical clavicle fracture fixation in patients with and without different degrees of associated CWI.Methods: A retrospective review over a four-year period of patients who underwent clavicle fracture repair was conducted. A CWI and no-CWI group were distinguished, and the CWI group was subdivided into the minor-CWI (three or fewer rib fractures without flail chest) and complex-CWI (flail chest, four or more rib fractures) subgroup. Demographic data, classification of the clavicle fracture, number of rib fractures, and associated injuries were recorded. Overall complications included surgery-related complications and unplanned hospital readmissions. Univariate analysis and stepwise backward multivariate logistic regression were used to identify potential risk factors for complications.Results: A total of 314 patients undergoing 316 clavicle fracture operations were studied; 28.7% of patients (90/314) occurred with associated CWI. Patients with associated CWI showed a significantly higher age, body mass index, and number of rib fractures. The overall and surgical-related complication rate were similar between groups. Unplanned 30-day hospital readmission rates were significantly higher in the complex-CWI group (p = 0.02). Complex CWI and number of rib fractures were both independent factor for 30-day unplanned hospital readmission (OR 1.59, 95% CI: 1.00-2.54 and OR 1.33, 95% CI: 1.06-1.68, respectively).Conclusion: CWI did not affect surgery-related complications after clavicle fracture repair. However, complex-CWI may increase 30-day unplanned hospital readmission rates. [ABSTRACT FROM AUTHOR]

Bacteria‐mediated tumor therapy (BMTT) has been known for decades; however, its clinical use is inhibited by its association with infections. To address this issue, a spiky, bacterium‐like metal–organic framework (MOF), which can replicate the functional responses of BMTT without its adverse side‐effects, is proposed. MOFs are synthesized in a solvothermal reaction of aluminum sulfate, ruthenium chloride hydrate, and 2‐aminoterephthalic acid; they have a spherical morphology or many nanospikes on their surfaces, depending on the reaction temperature. Both spherical and spiky MOFs can function as photothermal agents, converting absorbed optical energy into local heat. Owing to their higher surface area of interaction, spiky MOFs are more easily phagocytosed by macrophages than are spherical MOFs, strengthening their immune responses. Moreover, when injected intratumorally, spiky MOFs reside significantly longer than spherical ones, enabling their use in repeated photothermal treatments. The combination of in situ vaccination with intratumorally injected bacterium‐like MOFs under exposure to an near‐infrared laser and the immune checkpoint blockade of systemically administered αPD‐1 is evaluated in tumor‐bearing mice. The results indicate that the checkpoint blockade acts synergistically with in situ vaccination to provide diverse antitumor functions of BMTT, destroying a primary tumor and suppressing tumor recurrence and metastasis. [ABSTRACT FROM AUTHOR]

Abstract: Inflammation is involved in many human pathologies, including osteoarthritis (OA). Hydrogen (H2) is known to have anti‐inflammatory effects; however, the bioavailability of directly administered H2 gas is typically poor. Herein, a local delivery system that can provide a high therapeutic concentration of gaseous H2 at inflamed tissues is proposed. The delivery system comprises poly(lactic‐co‐glycolic acid) microparticles that contain magnesium powder (Mg@PLGA MPs). Mg@PLGA MPs that are intra‐muscularly injected close to the OA knee in a mouse model can act as an in situ depot that can evolve gaseous H2 continuously, mediated by the cycle of passivation/activation of Mg in body fluids, at a concentration that exceeds its therapeutic threshold. The analytical data that are obtained in the biochemical and histological studies indicate that the proposed Mg@PLGA MPs can effectively mitigate tissue inflammation and prevent cartilage from destruction, arresting the progression of OA changes. [ABSTRACT FROM AUTHOR]

Abstract: Inflammation is involved in many human pathologies, including osteoarthritis (OA). Hydrogen (H2) is known to have anti‐inflammatory effects; however, the bioavailability of directly administered H2 gas is typically poor. Herein, a local delivery system that can provide a high therapeutic concentration of gaseous H2 at inflamed tissues is proposed. The delivery system comprises poly(lactic‐co‐glycolic acid) microparticles that contain magnesium powder (Mg@PLGA MPs). Mg@PLGA MPs that are intra‐muscularly injected close to the OA knee in a mouse model can act as an in situ depot that can evolve gaseous H2 continuously, mediated by the cycle of passivation/activation of Mg in body fluids, at a concentration that exceeds its therapeutic threshold. The analytical data that are obtained in the biochemical and histological studies indicate that the proposed Mg@PLGA MPs can effectively mitigate tissue inflammation and prevent cartilage from destruction, arresting the progression of OA changes. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) resulting from the overexpression of drug transporters such as P-glycoprotein (Pgp) increases the efflux of drugs and thereby limits the effectiveness of chemotherapy. To address this issue, this work develops an injectable hollow microsphere (HM) system that carries the anticancer agent irinotecan (CPT-11) and a NO-releasing donor (NONOate). Upon injection of this system into acidic tumor tissue, environmental protons infiltrate the shell of the HMs and react with their encapsulated NONOate to form NO bubbles that trigger localized drug release and serve as a Pgp-mediated MDR reversal agent. The site-specific drug release and the NO-reduced Pgp-mediated transport can cause the intracellular accumulation of the drug at a concentration that exceeds the cell-killing threshold, eventually inducing its antitumor activity. These results reveal that this pH-responsive HM carrier system provides a potentially effective method for treating cancers that develop MDR. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) resulting from the overexpression of drug transporters such as P-glycoprotein (Pgp) increases the efflux of drugs and thereby limits the effectiveness of chemotherapy. To address this issue, this work develops an injectable hollow microsphere (HM) system that carries the anticancer agent irinotecan (CPT-11) and a NO-releasing donor (NONOate). Upon injection of this system into acidic tumor tissue, environmental protons infiltrate the shell of the HMs and react with their encapsulated NONOate to form NO bubbles that trigger localized drug release and serve as a Pgp-mediated MDR reversal agent. The site-specific drug release and the NO-reduced Pgp-mediated transport can cause the intracellular accumulation of the drug at a concentration that exceeds the cell-killing threshold, eventually inducing its antitumor activity. These results reveal that this pH-responsive HM carrier system provides a potentially effective method for treating cancers that develop MDR. [ABSTRACT FROM AUTHOR]

Background: Low concentrations of carbon monoxide (CO) have anti-inflammatory effects and can reduce bone erosion in a murine collagen-induced arthritis model. The objective of this study was to assess the effects of CO on receptor activator of NF-KB ligand (RANKL), one of the key stimulators of osteoclastogenesis. Methods: The in vivo effects of CO on RANKL expression were assessed in a collagen antibody-induced arthritis model in mice. Cell proliferation and apoptosis were assessed in the RAW246.7 cell line stimulated with RANKL and exposed to either air or CO. The number of tartrate resistant acid phosphatase (TRAP)- positive RAW246.7 cells was also examined after treatment with RANKL and the peroxisome proliferator-activated receptor gamma (PPARy) agonist, Troglitazone. Results: CO reduced RANKL expression in the synovium of arthritic mice. Although CO slightly increased RAW246.7 cell proliferation, no differences in activated caspase 3 levels were detected. In addition, Troglitazone ameliorated the inhibitory effects of CO on RANKL-induced TRAP expression by RAW246.7 cells. Conclusions: CO suppresses osteoclast differentiation by inhibiting the RANKL-induced activation of PPAR-y. Given the role of the PPAR-y/cFos (AP-1) pathway in regulating the transcription factor, NFATc1, the master regulator of osteoclastogenesis, further studies are warranted to explore CO in treating inflammatory bone disorders. [ABSTRACT FROM AUTHOR]