MyD88 exacerbates inflammation-induced bone loss by modulating dynamic equilibrium between Th17/Treg cells and subgingival microbiota dysbiosis.

BACKGROUND: This study aimed to investigate the contribution of myeloid differentiation primary-response gene 88 (MyD88) on the differentiation of T helper type 17 (Th17) and regulatory T (Treg) cells and the emerging subgingival microbiota dysbiosis in Porphyromonas gingivalis-induced experimental periodontitis. METHODS: Alveolar bone loss, infiltrated inflammatory cells, immunostained cells for tartrate-resistant acid phosphatase (TRAP), the receptor activator of nuclear factor-kB ligand (RANKL), and osteoprotegerin (OPG) were quantified by microcomputerized tomography and histological staining between age- and sex-matched homozygous littermates (wild-type [WT, Myd88+/+] and Myd88-/- on C57BL/6 background). The frequencies of Th17 and Treg cells in cervical lymph nodes (CLNs) and spleen were determined by flow cytometry. Cytokine expression in gingival tissues, CLNs, and spleens were studied by quantitative polymerase chain reaction (qPCR). Analysis of the composition of the subgingival microbiome and functional annotation of prokaryotic taxa (FAPROTAX) analysis were performed. RESULTS: P. gingivalis-infected Myd88-/- mice showed alleviated bone loss, TRAP+ osteoclasts, and RANKL/OPG ratio compared to WT mice. A significantly higher percentage of Foxp3+CD4+ T cells in infected Myd88-/- CLNs and a higher frequency of RORγt+CD4+ T cells in infected WT mice was noted. Increased IL-10 and IL-17a expressions in gingival tissue at D14-D28 then declined in WT mice, whereas an opposite pattern was observed in Myd88-/- mice. The Myd88-/- mice exhibited characteristic increases in gram-positive species and species having probiotic properties, while gram-negative, anaerobic species were noted in WT mice. FAPROTAX analysis revealed increased aerobic chemoheterotrophy in Myd88-/- mice, whereas anaerobic chemoheterotrophy was noted in WT mice after P. gingivalis infection. CONCLUSIONS: MyD88 plays an important role in inflammation-induced bone loss by modulating the dynamic equilibrium between Th17/Treg cells and dysbiosis in P. gingivalis-induced experimental periodontitis.

Underlying mechanisms of novel cuproptosis-related dihydrolipoamide branched-chain transacylase E2 (DBT) signature in sunitinib-resistant clear-cell renal cell carcinoma.

Renal cell carcinoma (RCC) is the predominant form of malignant kidney cancer. Sunitinib, a primary treatment for advanced, inoperable, recurrent, or metastatic RCC, has shown effectiveness in some patients but is increasingly limited by drug resistance. Recently identified cuproptosis, a copper-ion-dependent form of programmed cell death, holds promise in combating cancer, particularly drug-resistant types. However, its effectiveness in treating drug resistant RCC remains to be determined. Exploring cuproptosis's regulatory mechanisms could enhance RCC treatment strategies. Our analysis of data from the GEO and TCGA databases showed that the cuproptosis-related gene DBT is markedly under expressed in RCC tissues, correlating with worse prognosis and disease progression. In our study, we investigated copper CRGs in ccRCC, noting substantial expression differences, particularly in advanced-stage tumors. We established a connection between CRG expression levels and patient survival, positioning CRGs as potential therapeutic targets for ccRCC. In drug resistant RCC cases, we found distinct expression patterns for DBT and GLS CRGs, linked to treatment resistance. Our experiments demonstrated that increasing DBT expression significantly reduces RCC cell growth and spread, underscoring its potential as a therapeutic target. This research sheds new light on the role of CRGs in ccRCC and their impact on drug resistance.

Liaw's Ellipse Anteversion Method for Distinguishing Acetabular Component Retroversion from Anteversion on Plain Radiographs.

Improper acetabulum component position is a significant risk factor for postoperative dislocation after total hip arthroplasty. Several radiographic two-dimensional methods exist for measuring acetabulum component anteversion, but they cannot distinguish between anteversion and retroversion. "Liaw's version," initially proposed as a simple mathematical standardized two-dimensional method, was modified to the computerized ellipse method, proving superior accuracy to traditional two-dimensional methods. In this article, we demonstrated its application in detecting and measuring retroverted acetabulum component. We obtained anteroposterior pelvis radiographs from a patient undergoing total hip arthroplasty on the day of surgery and 2 weeks postoperatively. The computerized ellipse method was used to measure the acetabulum component orientation. Upon comparison, the difference between θ assigned to be retroverted (9.52-8.56 = 0.96) is much smaller than the difference between θ assigned to be anteverted (23.81-18.86 = 4.95), leading us to determine retroversion. This was further confirmed by computed tomography at the 6-week follow-up. We propose that using the computerized ellipse method to measure Liaw's version can be a valuable tool in identifying acetabulum component retroversion on anteroposterior radiographs during routine postoperative follow-up and retrospective assessments of total hip arthroplasty patients.

Influence of body mass index on severity of rotator cuff tears.

BACKGROUND: Research on the relationship between obesity and rotator cuff tears (RCTs) has been limited to the impact of obesity on the results of arthroscopic repair of RCTs; thus, a need for rigorous research controlling for other factors affecting RCTs is warranted, especially to better understand the impact of body mass index (BMI) on RCT severity. METHODS: A retrospective study of admission records contained in electronic medical records pertaining to patients who were admitted for RCT repair on 1 shoulder between January 2018 and July 2022 was conducted. In total, 386 patients were included. In accordance with guidance regarding obesity from Taiwan's Ministry of Health and Welfare, patients were divided into three groups: underweight or normal weight (BMI <24.0 kg/m2), overweight (BMI 24.0-26.9 kg/m2), or obese (BMI ≥27.0 kg/m2). Magnetic resonance imaging was used to assess RCT severity in terms of four parameters: Patte stage (PS), fatty infiltration (FI), anteroposterior tear size (AP), and retraction size. Multinomial logistic regression analysis was performed on PS and FI grade data, and multiple linear regression analysis was performed on AP tear size and retraction size in order to analyze impact. RESULTS: Our results revealed that the average age of the 386 patients was 63.41 years (SD = 9.29) and the mean BMI was 25.88 (SD = 3.72) kg/m2. We found significant differences in PS (P = .003), FI (P < .001), retraction size (P = .001), and AP tear size (P = .001) among patients who were underweight or normal weight, overweight, and obese. After controlling for other risk factors, including age, gender, RCT-prone occupation, duration of shoulder pain prior to surgery, history of shoulder injury, and tobacco use, we found that obese patients had higher severity levels in PS (B = 1.21, OR = 3.36, P = .029), FI (B = 1.38, OR = 3.96, P < .001), retraction size (ß = 0.18, P = .001), and AP tear size (ß = 0.18, P = .001) compared to underweight or normal weight patients. CONCLUSIONS: Our study demonstrates that a correlation exists between BMI-measured obesity and RCT severity. We therefore suggest that adults control their weight given that maintaining a healthy weight is highly associated with better shoulder health.

Correlation between Subchondral Insufficiency Fracture of the Knee and Osteoarthritis Progression in Patients with Medial Meniscus Posterior Root Tear.

A medial meniscus posterior root tear (MMPRT) contributes to knee joint degeneration. Arthroscopic transtibial pullout repair (ATPR) may restore biomechanical integrity for load transmission. However, degeneration persists after ATPR in certain patients, particularly those with preoperative subchondral insufficiency fracture of the knee (SIFK). We explored the relationship between preoperative SIFK and osteoarthritis (OA) progression in retrospectively enrolled patients who were diagnosed as having an MMPRT and had received ATPR within a single institute. Based on their preoperative magnetic resonance imaging (MRI), these patients were then categorized into SIFK and non-SIFK groups. OA progression was evaluated by determining Kellgren-Lawrence (KL) grade changes and preoperative and postoperative median joint widths. SIFK characteristics were quantified using Image J (Version 1.52a). Both groups exhibited significant post-ATPR changes in medial knee joint widths. The SIFK group demonstrated significant KL grade changes (p < 0.0001). A larger SIFK size in the tibia and a greater lesion-to-tibia length ratio in the coronal view were positively correlated with more significant KL grade changes (p = 0.008 and 0.002, respectively). Thus, preoperative SIFK in patients with an MMPRT was associated with knee OA progression. Moreover, a positive correlation was observed between SIFK lesion characteristics and knee OA progression.

Mapping out the bibliometric characteristics of classic articles published in a Taiwanese academic journal in dentistry: A scopus-based analysis.

Background/purpose: Since its inception, the Journal of Dental Sciences (JDS) has aimed to publish quality articles relevant to all fields in dentistry. The purpose of this study was to analyze the bibliometric characteristics and dissected associated factors correlated with citation counts of classic articles published in the JDS. Materials and method: Scopus® database was used to search the qualified articles published in JDS from 2009 to 2021. The bibliometric parameters, including journal impact factor (JIF), self-citation, study design, research field, geographic, country and institute of origin, inter-institute, inter-nation collaboration, keywords hotness and associated factors correlated with citation counts of classic articles were analyzed. Results: One hundred and eight articles from Scopus® database were eligible for analysis. The citation counts of classic articles ranged from 12 to 192, the average citation was 22.02. The most common study design was the in vitro/in vivo, followed by the cross-sectional study, and the major research field were Dental Materials. The most productive country and institute is Taiwan, and Chung Shan Medical University, respectively. The trend of inter-institute (71.03%) and inter-nation (11.22%) collaboration steadily increased since 2009. By using the multivariable linear regression model, Preventive and Community Dentistry in the research field significantly increased the citation counts. Conclusion: Despite its limitations, the escalating trends in JIFs, and JIFs without self-citations, and inter-nation and inter-institute collaboration of classic articles were noticed. Of all the dissected associated factors, Preventive and Community Dentistry in the research field significantly increased the citation counts of classic article.

Bioinspired and self-restorable alginate-tyramine hydrogels with plasma reinforcement for arthritis treatment.

Long-standing administration of disease-modifying antirheumatic drugs confirms their clinical value for managing rheumatoid arthritis (RA). Nevertheless, there are emergent worries over unwanted adverse risks of systemic drug administration. Hence, a novel strategy that can be used in a drug-free manner while diminishing side effects is immediately needed, but challenges persist in the therapy for RA. To this end, herein we conjugated tyramine (TYR) with alginate (ALG) to form ALG-TYR and then treated it for 5 min with oxygen plasma (ALG-TYR + P/5 min). It was shown that the ALG-TYR + P/5 min hydrogel exhibited favorable viscoelastic, morphological, mechanical, biocompatible, and cellular heat-shock protein amplification behaviors. A thorough physical and structural analysis was conducted on the ALG-TYR + P/5 min hydrogel, revealing favorable physical characteristics and uniform porous structural features within the hydrogel. Moreover, ALG-TYR + P/5 min not only effectively inhibited inflammation of RA but also potentially regulated lesion immunity. Once ALG-TYR + P/5 min was intra-articularly administered to joints of rats with zymosan-induced arthritis, we observed that ALG-TYR + P/5 min could ameliorate syndromes of RA joint. This bioinspired and self-restorable ALG-TYR + P/5 min hydrogel can thus serve as a promising system to provide prospective outcomes to potentiate RA therapy.

Complement components C3b and C4b as potential reliable site-specific diagnostic biomarkers for periodontitis.

OBJECTIVE: This study aimed to investigate the correlation between the expression levels of C3b and C4b in human gingival tissue (GT) and gingival crevicular fluid (GCF) and disease severity in human periodontitis and to determine whether C3b and C4b are significant site-specific complementary diagnostic markers for periodontitis. BACKGROUND: A variety of biomarkers that have potential for informing diagnoses of periodontitis have been proposed. The complement components C3b and C4b were found to be positively correlated with disease severity. The therapeutic effect of targeting C3b and C4b on inflammatory bone loss in experimental periodontitis models has been studied. However, studies on the diagnostic potential of the gingival C3b and C4b expression levels for periodontitis are scarce. METHODS: The expression levels of C3b and C4b in the GT and GCF were investigated via immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The correlation between the expression levels of C3b and C4b and disease severity with probing depth as well as the clinical attachment level were determined. To evaluate the diagnostic accuracy of the C3b and C4b expression levels at the periodontitis sites, the receiver operating characteristic (ROC) curve, cut-off point, area under the ROC curve, sensitivity, and specificity were analyzed. RESULTS: The expression levels of C3b and C4b in human GT and GCF were significantly positively correlated with periodontitis severity. The expression levels of combined C3b + C4b in the GT can significantly differentiate the disease status at the tissue level (p < .0001). Similarly, the expression levels of C3b + C4b in GCF can statistically distinguish periodontitis sites from healthy ones (p < .0001). CONCLUSIONS: Locally deposited C3b and C4b were positively correlated with periodontitis severity and recognized as site-specific diagnostic biomarkers for clinicopathological features in periodontitis. The association between the C3b and C4b network and periodontitis may be further understood and provide a basis for the development of novel screening as well as diagnostic and therapeutic strategies for periodontitis.

The referral pattern and treatment modality for peri-implant disease between periodontists and non-periodontist dentists.

OBJECTIVES: This study is to investigate the referral pattern and treatment modality of dentists in the management of peri-implant diseases between periodontists and non-periodontist dentists (NPDs). MATERIALS AND METHODS: A total of 167 validated questionnaires were obtained from periodontists and NPDs, who had experience of placing implants for at least one year. Question I to IV asked how the dentist would respond if a patient came for treatment of their peri-implant diseases with four different scenarios according to resource of patient and disease severity. For each Scenario, dentists also replied which treatment procedures they would use if they decide to treat the patient. RESULTS: Periodontal training, resource of patient, and disease severity were shown to significantly influence the referral pattern and treatment modality in the management of peri-implant disease (p < 0.05). Periodontists were more likely to use variable treatment procedures, including occlusal adjustment (OR = 2.283, p < 0.01), oral hygiene instruction (OR = 3.751, p < 0.001), topical antiseptic agent (OR = 2.491, p < 0.005), non-surgical mechanical therapy (OR = 2.689, p < 0.001), surgical therapy (OR = 2.009, p < 0.01), and remove implant (OR = 3.486, p < 0.001) to treat peri-implant diseases, compared to NPDs. CONCLUSION: The periodontal specialty training, resource of patient, and disease severity significantly influenced the referral pattern and treatment modality of dentist treating an implant diagnosed with peri-implant disease. This study also highlighted the importance of educating basic periodontal and peri-implant disease-related knowledge to all dentists regularly performing dental implant treatments. CLINICAL RELEVANCE: Peri-implant diseases are highly prevalent among patients with dental implants. Periodontal specialty training could enhance using variable treatment procedures to treat peri-implant diseases for dentists.

Immunologic, Anti-Inflammatory, and Anti-Muscle Damage Profile of Supplemented Vitamin D3 in Healthy Adults on Strenuous Endurance Exercise.

Reportedly, strenuous endurance exercise can depress the immune system and induce inflammation and muscle damage. Therefore, this double-blinded, matched-pair study aimed to investigate the impact of vitamin D3 supplementation on immune response (leukocyte, neutrophil, lymphocyte, CD4+, CD8+, CD19+, and CD56+ counts), inflammatory profile (TNF-α and IL-6), muscle damage (CK and LDH levels), as well as aerobic capacity after strenuous endurance exercise in 18 healthy men taking 5000 IU of vitamin D3 (n = 9) or placebo (n = 9) daily for 4 weeks. Total and differential blood leukocyte counts, levels of cytokines, and muscle damage biomarkers were determined before, immediately after, and 2, 4, and 24 h after exercise. The IL-6, CK, and LDH levels were significantly lower in vitamin D3 group at 2, 4, and 24 h post exercise (p < 0.05). Maximal and average heart rates during exercise were also significantly lower (p < 0.05). In the vitamin D3 group, the CD4+/CD8+ ratio after 4 weeks of supplementation was only significantly lower at post-0 than at baseline and significantly higher at post-2 than at baseline and post-0 (all p < 0.05). Taken together, 5000 IU of daily vitamin D3 supplementation for 4 weeks exhibited positive effects in terms of increased blood 25(OH)D levels, CD4+/CD8+ ratio (immune response), and aerobic capacity while inhibiting inflammatory cytokines and CK and LDH (muscle damage) in people performing strenuous endurance exercise.

Biomechanical comparisons of dynamic fixators with rod-rod and screw-spacer joints on lumbar hybrid fixation.

BACKGROUND: Hybrid fixators with quite different joint design concepts have been widely to suppress adjacent segment degeneration problems. The kinematic and kinetic responses of the adjacent and transition segments and contact behaviors at the bone-screw interfaces served as the objective of this study. METHODS: The moderately degenerated L4/L5 and mildly degenerative L3/L4 segments were respectively immobilized by a static fixator and further bridged by the rod-rod (Isobar) and screw-spacer (Dynesys) fixator. The joint stiffness and mobility of the rod-rod system and the cable pretension of the screw-spacer system were systematically varied. FINDINGS: The flexion of the screw-spacer system provided higher mobility to the transition segment, reducing adjacent-segment problems. The cable pretension had a minor effect on the construct behavior. However, due to limited joint mobility, the rod-rod system showed higher constraints to the transition segment and induced more adjacent-segment compensations. The increased mobility of the rod-rod joint caused it to behave as a more dynamic fixator that increased adjacent-segment compensations at the transition segment. Comparatively, increasing the joint mobility showed more significant effects on the construct behaviors than decreasing the joint stiffness. Furthermore, increased constraint by the rod-rod joint induced higher stress and risk of loosening at the bone-screw interfaces INTERPRETATION: If the protection of the transition segment is the major concern, the rod-rod system can be used to constrain the intervertebral motion and share the higher loads through the fixator. Otherwise, the screw-spacer system is recommended in situations where higher loads onto the transition disc are allowable.

Platelet-Rich Fibrin-Augmented Gap-Bridging Strategy in Rabbit Anterior Cruciate Ligament Repair.

BACKGROUND: We assessed the efficacy of a novel platelet-rich fibrin (PRF)-augmented repair strategy for promoting biological healing of an anterior cruciate ligament (ACL) midsubstance tear in a rabbit model. The biological gap-bridging effect of a PRF scaffold alone or in combination with rabbit ligamentocytes on primary ACL healing was evaluated both in vitro and in vivo. HYPOTHESIS: A PRF matrix can be implanted as a provisional fibrin-platelet bridging scaffold at an ACL defect to facilitate functional healing. STUDY DESIGN: Controlled laboratory study. METHODS: The biological effects of PRF on primary rabbit ligamentocyte proliferation, tenogenic differentiation, migration, and tendon-specific matrix production were investigated for treatment of cells with PRF-conditioned medium (PRFM). Three-dimensional (3D) lyophilized PRF (LPRF)-cell composite was fabricated by culturing ligamentocytes on an LPRF patch for 14 days. Cell-scaffold interactions were investigated under a scanning electron microscope and through histological analysis. An ACL midsubstance tear model was established in 3 rabbit groups: a ruptured ACL was treated with isolated suture repair in group A, whereas the primary repair was augmented with LPRF and LPRF-cell composite to bridge the gap between ruptured ends of ligaments in groups B and C, respectively. Outcomes-gross appearance, magnetic resonance imaging, and histological analysis-were evaluated in postoperative weeks 8 and 12. RESULTS: PRFM promoted cultured ligamentocyte proliferation, migration, and expression of tenogenic genes (type I and III collagen and tenascin). PRF was noted to upregulate cell tenogenic differentiation in terms of matrix production. In the 3D culture, viable cells formed layers at high density on the LPRF scaffold surface, with notable cell ingrowth and abundant collagenous matrix depositions. Moreover, ACL repair tissue and less articular cartilage damage were observed in knee joints in groups B and C, implying the existence of a chondroprotective phenomenon associated with PRF-augmented treatment. CONCLUSION: Our PRF-augmented strategy can facilitate the formation of stable repair tissue and thus provide gap-bridging in ACL repair. CLINICAL RELEVANCE: From the translational viewpoint, effective primary repair of the ACL may enable considerable advancement in therapeutic strategy for ACL injuries, particularly allowing for proprioception retention and thus improved physiological joint kinematics.

Synergistic disruption of BTK and BCL-2 causes apoptosis while inducing ferroptosis in double-hit lymphoma.

Double-hit lymphoma (DHL) is an aggressive subset of Diffuse Large B-cell Lymphoma (DLBCL) with poor outcomes and without satisfying treatment options. BTK inhibitor monotherapy is ineffective to suppress aggressive lymphoma. Hence, combination with other potential agents is warranted. Here, we demonstrated the second generation of BTK inhibitor, zanubrutinib, and a BCL-2 inhibitor, navitoclax, worked in synergistic manner to suppress DHL. Comprehensive in silico approach by interrogating single-cell to bulk-level profiling was employed along with in vitro and in vivo validation in DHL cell lines. Ablation of BTK enhanced sensitivity to navitoclax and suppressed proliferation of DHL cells. Combination of second generation of BTK inhibitor with navitoclax synergistically suppressed DLBCL cells with higher synergy score in DHL subset. The drug combination triggered apoptosis and ferroptosis, with the latter being characterized by reactive oxygen species (ROS) accumulation, extensive lipid peroxidation, and depletion of reduced glutathione. Moreover, ablation of BTK sensitized DHL cells to ferroptosis. Mechanistically, disruption of BTK and BCL-2 triggered ferroptosis by downregulating NRF2 and HMOX1, while deactivating GPX4. Combination of zanubrutinib and navitoclax effectively suppressed tumor growth in vivo. Our data suggest that zanubrutinib and navitoclax synergistically suppressed DHL by inducing apoptosis and ferroptosis.

Targeting therapeutic agent against C3b/C4b, SB002, on the inflammation-induced bone loss in experimental periodontitis.

AIMS: To use experimental periodontitis models in rats to investigate the correlation between local expression of the complement components C3b and C4b in periodontal tissues and disease severity, and to assess the therapeutic effects of targeting C3b/C4b on inflammatory bone loss. MATERIALS AND METHODS: The gingival expression of C3, C3b, and C4b in animal experimental periodontitis models were analysed immunohistochemically. The therapeutic effects of the C3b/C4b inhibitor (SB002) on ligation-induced experimental periodontitis was examined using biochemical, histological, and immunohistochemical analyses. RESULTS: The gingival expression levels of C3, C3b, and C4b were positively correlated with the severity of periodontitis. Moreover, both single and multiple injections of the C3b/C4b inhibitor had preventive and therapeutic effects on alveolar bone loss in ligation-induced experimental periodontitis with no associated adverse consequences. CONCLUSIONS: The association between C3b/C4b and periodontitis may provide a basis for the development of novel therapeutic strategies for periodontitis and other inflammatory diseases.

Comparison of Locking-Loop Suture Bridge Repair and Single-Row Suture Anchor Repair in Small to Medium Rotator Cuff Tears: A Prospective Cohort Study With Clinical and Ultrasound Evaluations.

Background: Single-row (SR) and double-row repair techniques have been described to treat rotator cuff tears. We present a novel surgical strategy of arthroscopic-assisted mini-open repair in which a locking-loop suture bridge (LLSB) is used. Purpose: To compare the functional outcomes and repair integrity of LLSB technique to the SR technique for arthroscopic-assisted mini-open repair of small to medium rotator cuff tears. Study Design: Cohort study; Level of evidence, 3. Methods: Included were 39 patients who underwent LLSB repair (LLSB group) and 44 patients who underwent SR suture anchor repair (SR group) from 2015 to 2018. We evaluated all patients preoperatively and at 3, 6, 12, and 24 months postoperatively using the visual analog scale (VAS) for pain, Oxford Shoulder Score (OSS), and American Shoulder and Elbow Surgeons (ASES) score. Also, shoulder sonography was performed at 12 months postoperatively to evaluate repair integrity using the Sugaya classification system. The independent-sample t test was used to analyze functional outcomes (VAS, OSS, and ASES scores), and the Fisher exact test was used to analyze postoperative sonography results. Results: Patients in both the LLSB and SR groups saw a significant improvement on all 3 outcome measures from preoperatively to 24 months postoperatively (P < .001 for all). However, when comparing scores between groups, only the scores at 3 months postoperatively differed significantly (VAS: P = .002; OSS: P < .001; ASES: P = .005). Shoulder sonography at 12 months postoperatively revealed no significant difference in repair integrity between the LLSB and SR groups (retear rate: 10.26% and 6.82%, respectively; P = .892). Conclusion: Better outcome scores were seen at 3-month follow-up in the LLSB group, with no difference in retear rates compared with the SR group at 12 months postoperatively. The LLSB technique was found to be a reliable technique for rotator cuff repair of small- to medium-sized tears.

Silibinin alleviates inflammation-induced bone loss by modulating biological interaction between human gingival fibroblasts and monocytes.

BACKGROUND: Silibinin has shown various pharmacological effects that could be attributed to its antioxidant, anti-inflammatory, and immunoregulatory properties. However, the therapeutic potential of silibinin for periodontitis has not been investigated. METHODS: The therapeutic effects of silibinin in ligation-induced experimental periodontitis were investigated using biochemical, histological, and immunohistochemical methods. The effects of silibinin on the osteoclastogenesis of RAW264.7 cells were investigated using TRAP staining, quantitative polymerase chain reaction (qPCR), pit formation, and immunoblotting. Moreover, its effects on inflammatory cytokine production, RANKL expression, and oxidative stress in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (HGFs) were evaluated using qPCR and flow cytometry. A coculture system was established to elucidate the effects of silibinin on the crosstalk between LPS-stimulated HGFs and undifferentiated monocytes. RESULTS: Silibinin significantly reduced the alveolar bone loss, decreased the gingival inflammation and RANKL expression, and decreased the RANKL/osteoprotegerin ratio in gingival tissues in experimental periodontitis. The in vitro results showed that silibinin inhibited RANKL-induced osteoclast differentiation and function of RAW264.7 cells and suppressed RANKL-induced nuclear factor of activated T cells 1 (NFATc1) induction and translocation through the nuclear factor-κB and mitogen-activated protein kinase signaling pathways. Silibinin decreased the inflammatory cytokine level and oxidative stress production in LPS-stimulated HGFs; significantly suppressed membrane-bound RANKL expression on LPS-stimulated HGFs; and significantly disrupted TRAP+ cell differentiation in the coculture system. CONCLUSIONS: Silibinin effectively inhibits inflammation-induced bone loss in experimental periodontitis based on the regulation of stimulated HGFs by inhibiting the expression of inflammatory and osteoclastogenic mediators. Collectively, targeting the inflamed HGF resolution that mediates osteogenesis may use silibinin as a potential drug-repurposing candidate for modulating alveolar bone destruction in periodontitis. SUMMARY: Silibinin effectively inhibits inflammation-induced bone loss in experimental periodontitis based on the regulation of stimulated HGFs by inhibiting the expression of inflammatory and osteoclastogenic mediators.

Retrospective study on the factors influencing the severity of pressure injuries among intensive care unit patients.

AIMS AND OBJECTIVES: This study investigated the factors of pressure injuries in patients in intensive care units (ICU). BACKGROUND: Pressure injuries among patients in ICUs can be prevented by the early assessment of risk factors and taking appropriate preventative measures. DESIGN: A retrospective study. METHODS: ICU patients who suffered from pressure injuries between January 2016 and August 2018 at a hospital in Taiwan were selected. Patient medical histories and data associated with pressure injuries and medical treatment were collected from electronic medical records. A total of 256 patients were included in our analysis. The study adhered to the STROBE checklist. RESULTS: A multivariate model of multinomial logistic regression analysis indicated that when compared to Stage 1 pressure injuries, Stage 2-4 pressure injuries were associated with albumin levels. Patients with lower albumin levels were at greater odds of Stage 2-4 pressure injuries than Stage 1 pressure injuries. In addition, when compared to unstageable pressure injuries or deep tissue injuries, Stage 1 pressure injuries were associated with the use of fentanyl and haemoglobin levels. Patients using fentanyl were more likely to suffer from unstageable pressure injuries, and those with lower haemoglobin levels were more likely to suffer from unstageable pressure injuries or deep tissue injuries. CONCLUSION: When patients were simultaneously on ventilators and taking midazolam or fentanyl, the incidence of pressure injuries with greater severity became higher. Furthermore, ICU patients with lower albumin and haemoglobin levels were more likely to suffer from pressure injuries of greater severity. RELEVANCE TO CLINICAL PRACTICE: For critically ill patients on ventilators, it is recommended to devise a means of assessing each patient daily as well as systematically reduce their dosage of midazolam or fentanyl. Furthermore, regularly monitoring albumin and haemoglobin levels to understand their nutritional status is necessary.

Extrinsic factors of pressure injuries in patients during surgery: A frequency matched retrospective study.

This study was to clarify the connection between extrinsic factors and the risk of perioperative pressure injuries (PIs) through the case-control approach, which involved making the intrinsic factors of the patients in the control group with no PIs consistent with those of the case group with PIs. We collected samples from a teaching hospital in Taiwan. We found a total of 132 patients deemed to have developed perioperative PIs. Using 1:2 frequency matching, we matched these cases with patients who had not developed PIs by gender, age, and BMI. Binary logistic regression analysis of the odds ratios of the extrinsic factors and PI risk revealed that the independent variables with statistical significance included duration of anaesthesia 3 h, amount of blood loss, use of electric blankets, diastolic blood pressure below 60 mmHg during surgery, and oxyhemoglobin saturation by pulse oximetry (SPO2 ) below 93% during surgery. Emphasis should be placed on cooperation among the medical team during surgery, less use of electric blankets, control over the duration of anaesthesia and blood loss, continuous monitoring of the patient during surgery for any emergencies, and the maintenance of patient diastolic blood pressure and blood oxygen levels to reduce the risk of PIs.

Therapeutic targeting of hepatocellular carcinoma cells with antrocinol, a novel, dual-specificity, small-molecule inhibitor of the KRAS and ERK oncogenic signaling pathways.

Until recently, sorafenib has been the only treatment approved by the U.S. Food and Drug Administration for patients with advanced hepatocellular carcinoma (HCC). Some patients, however, exhibit resistance to this treatment and subsequently experience cancer progression, recurrence, or death. Therefore, identifying a new alternative treatment for patients with little or no response to sorafenib treatment is vital. In this study, we explored the therapeutic potential and underlying molecular mechanism of antrocinol ((3aS,4R,6aS,10aR)-4-(hydroxymethyl)-7,7-dimethyldecahydro-1H-naphtho[1,8a-c]furan-1-one) in patients with HCC. The results indicated that antrocinol was more therapeutically effective than antrocin, Stivarga, and sorafenib against HCC cell lines. Antrocinol also substantially suppressed the expression of KRAS-GTP, p-MEK1/2, p-ERK1/2, and p-AKT in the Huh7 cell line. Additionally, antrocinol-induced apoptosis in the Huh7 cell line, inhibited the formation of tumorspheres, and suppressed the expression of cancer stem cell markers CD133, KLF4, CD44, OCT4, SOX2, and c-Myc. Animal studies revealed that antrocinol alone considerably suppressed tumor growth in nonobese diabetic/severe combined immunodeficient mice inoculated with Huh7 tumorspheres. It also synergistically enhanced the anticancer effect of sorafenib, resulting in enhanced suppression of tumor growth (p < 0.001) and tumorsphere formation (p < 0.001). In tumor samples resected from mice treated with antrocinol alone or in combination with sorafenib, immunohistochemical analysis revealed an increase in BAX expression and a decrease in ERK and AKT protein expression. To the best of our knowledge, this is the first report of the anti-HCC activity of antrocinol. With its higher therapeutic efficacy than that of sorafenib, antrocinol is a candidate drug for patients with HCC who demonstrate little or no response to sorafenib treatment.

Comparison of two different types of hybrid Tibial fixations for anterior cruciate ligament reconstruction: a prospective comparative cohort study.

BACKGROUND: Previous studies have compared different kinds of fixations for anterior cruciate ligament reconstruction. Nevertheless, there is no optimal method to date. To the best of authors' knowledge, there is no article discussing the combination of adjustable suspensory device and interference screw for hybrid tibial fixation. METHODS: In total, 66 patients (n = 34, adjustable suspensory device and interference screw; n = 32, cortical screw and interference screw) were analyzed. Their International Knee Documentation Committee score and Tegner activity level scale were evaluated before and after a 2-year follow-up. The Single Assessment Numeric Evaluation score was evaluated after a 2-year follow-up. Physical exams such as range of motion, anterior knee pain (VAS > = 3) and Lachman test were assessed before and at least 12 months after surgery. To evaluate tunnel widening, anteroposterior and lateral view radiography was conducted 1 day and at least 12 months after surgery. A more than 10% change was considered tibial tunnel widening. Mann-Whitney U test, independent t test, paired t test, Fisher's exact test and chi-squared test were used to compare the variables. Linear and logistic regression models were applied to adjust for potential confounders. RESULTS: No variable except gender (P = 0.006) showed significant difference with regard to demographic data. After adjustment, there was no statistically significant difference between the groups regarding post-operative physical exams. Patients who used adjustable suspensory device and interference screw had lower post-operative Single Assessment Numeric Evaluation score (adjusted ß - 8.194; P = 0.017), Tegner activity level scale (adjusted ß - 1.295; P = 0.001) and pre-operative degrees of knee flexion (adjusted ß - 2.825; P = 0.026). Less percentage of tunnel widening in the lateral view of radiographs was seen in patients in group of adjustable suspensory device and interference screw (adjusted ß - 1.733; P = 0.038). No significant difference was observed in the anteroposterior view of radiographs (adjusted ß - 0.667; P = 0.26). CONCLUSION: In these 66 patients, we observed less tibial tunnel widening and lower post-operative functional scores in the group of adjustable suspensory device and interference screw. Both groups displayed similar outcomes of physical exams as well as improvement after operation. The proposed method may become an alternative option. Nonetheless, the quality of our study is still limited, and thus further studies are warranted to determine the efficacy and further application. TRIAL REGISTRATION: Joint Institutional Review Board of Taipei Medical University, Taipei, Taiwan (No: N201805094 ). STUDY DESIGN: Prospective comparative cohort study; Level of evidence, II.