Inhibiting Bruton's Tyrosine Kinase to Counteract Chemoresistance and Stem Cell-Like Properties in Osteosarcoma.

Osteosarcoma, a highly aggressive bone cancer, often develops resistance to conventional chemotherapeutics, leading to poor prognosis and survival rates. The malignancy and chemoresistance of osteosarcoma pose significant challenges in its treatment, highlighting the critical need for novel therapeutic approaches. Bruton's tyrosine kinase (BTK) plays a pivotal role in B-cell development and has been linked to various cancers, including breast, lung, and oral cancers, where it contributes to tumor growth and chemoresistance. Despite its established importance in these malignancies, the impact of BTK on osteosarcoma remains unexplored. Our study delves into the expression levels of BTK in osteosarcoma tissues by data from the GEO and TCGA database, revealing a marked increase in BTK expression compared with primary osteoblasts and a potential correlation with primary site progression. Through our investigations, we identified a subset of osteosarcoma cells, named cis-HOS, which exhibited resistance to cisplatin. These cells displayed characteristics of cancer stem cells (CSCs), demonstrated a higher angiogenesis effect, and had an increased migration ability. Notably, an upregulation of BTK was observed in these cisplatin-resistant cells. The application of ibrutinib, a BTK inhibitor, significantly mitigated these aggressive traits. Our study demonstrates that BTK plays a crucial role in conferring chemoresistance in osteosarcoma. The upregulation of BTK in cisplatin-resistant cells was effectively countered by ibrutinib. These findings underscore the potential of targeting BTK as an effective strategy to overcome chemoresistance in osteosarcoma treatment.

The relationships between physical function, nutrition, cognitive function, depression, and sleep quality for facility-dwelling older adults with dynapenia.

BACKGROUND: The growing population of older adults worldwide is associated with an extended life expectancy and an increasing proportion of older adults with dynapenia. Most research on dynapenia has involved only populations of older adults living in the community; little research has examined the effects of risk factors on sleep quality among older adults with dynapenia residing in assisted living facilities. AIM: This study examined the relationships among physical function, nutrition, cognitive function, depression, and sleep quality among older adults with dynapenia residing in assisted living facilities. METHODS: In this cross-sectional study, data on physical function, nutrition, cognitive function, depression, and sleep quality was collected from 178 older adults with dynapenia residing in assisted living facilities, who were selected using purposive sampling. Descriptive statistical analysis, independent-sample t tests, chi-squared tests, and logistic regression analysis were performed using SPSS 25.0. RESULTS: The statistical analyses revealed correlations between sleep quality and age (t = 2.37, p < 0.05), level of education (χ2 = 3.85, p < 0.05), grip strength (t = 3.40, p < 0.01), activities of daily living (t = 4.29, p < 0.001), instrumental activities of daily living (t = 2.23, p < 0.001), calf circumference (t = 2.89, p < 0.01), Mini Nutritional Assessment scores (t = 2.29, p < 0.05), Mini Mental State Exam (MMSE) scores (t = 4.50, p < 0.001), and Geriatric Depression Scale (GDS) scores (t = - 4.20, p < 0.001). Calf circumference (OR = 0.8, 95% CI = 0.650.97, p < 0.05), GDS score (OR = 1.42, 95% CI = 1.05-1.92, p < 0.05), and MMSE score (OR = 0.85, 95% CI = 0.73-0.97, p < 0.05) were related to sleep quality among the sample population. CONCLUSION: Physical function, nutrition, cognitive function, and depression affect the sleep quality of older adults with dynapenia residing in assisted living facilities. Facility nurses must regularly assess these aspects of their patients to ensure that facility-dwelling older adults can maintain their physical function and improve their health to improve the quality of their sleep.

Interleukin-11/gp130 upregulates MMP-13 expression and cell migration in OSCC by activating PI3K/Akt and AP-1 signaling.

Oral squamous cell carcinoma (OSCC) is an extremely common head and neck cancer with a poor 5-year survival rate, especially in cases of metastatic disease. Interleukin (IL)-11 reportedly promotes cell growth and the epithelial-mesenchymal transition process in metastasis. However, the molecular mechanisms of IL-11 in OSCC metastasis are unclear. This study found that IL-11 upregulates matrix metalloproteinase 13 (MMP-13) expression in OSCC via the IL-11 receptor alpha subunit/glycoprotein 130 receptors that activate phosphatidyl-inositol 3-kinase, Ak strain transforming, and activator protein 1 signaling, which subsequently enhance MMP-13-induced tumor metastasis. TIMER2.0 analysis revealed a positive correlation between MMP-13 and IL-11 levels (r = 0.454). Moreover, a strong positive association was observed between higher levels of IL-11 expression in OSCC tissue (p < 0.01), lymph node metastasis (p = 0.0154), and clinical disease stage (p = 0.0337). IL-11 knockdown suppressed the migration of OSCC cells (p < 0.05). The evidence indicates that IL-11 can serve as a new molecular therapeutic target in OSCC metastasis.

Melatonin suppresses the metastatic potential of osteoblastic prostate cancers by inhibiting integrin α2 ß1 expression.

Advanced prostate cancer often develops into bone metastasis, which is characterized by aberrant bone formation with chronic pain and lower chances of survival. No treatment exists as yet for osteoblastic bone metastasis in prostate cancer. The indolamine melatonin (N-acetyl-5-methoxytryptamine) is a major regulator of the circadian rhythm. Melatonin has shown antiproliferative and antimetastatic activities but has not yet been shown to be active in osteoblastic bone lesions of prostate cancer. Our study investigations reveal that melatonin concentration-dependently decreases the migratory and invasive abilities of two osteoblastic prostate cancer cell lines by inhibiting FAK, c-Src, and NF-κB transcriptional activity via the melatonin MT1 receptor, which effectively inhibits integrin α2 ß1 expression. Melatonin therapy appears to offer therapeutic possibilities for reducing osteoblastic bone lesions in prostate cancer.

Melatonin Inhibits Osteoclastogenesis and Osteolytic Bone Metastasis: Implications for Osteoporosis.

Osteoblasts and osteoclasts are major cellular components in the bone microenvironment and they play a key role in the bone turnover cycle. Many risk factors interfere with this cycle and contribute to bone-wasting diseases that progressively destroy bone and markedly reduce quality of life. Melatonin (N-acetyl-5-methoxy-tryptamine) has demonstrated intriguing therapeutic potential in the bone microenvironment, with reported effects that include the regulation of bone metabolism, acceleration of osteoblastogenesis, inhibition of osteoclastogenesis and the induction of apoptosis in mature osteoclasts, as well as the suppression of osteolytic bone metastasis. This review aims to shed light on molecular and clinical evidence that points to possibilities of melatonin for the treatment of both osteoporosis and osteolytic bone metastasis. It appears that the therapeutic qualities of melatonin supplementation may enable existing antiresorptive osteoporotic drugs to treat osteolytic metastasis.

CCL4 Stimulates Cell Migration in Human Osteosarcoma via the mir-3927-3p/Integrin αvß3 Axis.

Osteosarcoma is the most common type of primary malignant bone cancer, and it is associated with high rates of pulmonary metastasis. Integrin αvß3 is critical for osteosarcoma cell migratory and invasive abilities. Chemokine (C-C motif) ligand 4 (CCL4) has diverse effects on different cancer cells through its interaction with its specific receptor, C-C chemokine receptor type 5 (CCR5). Analysis of mRNA expression in human osteosarcoma tissue identified upregulated levels of CCL4, integrin αv and ß3 expression. Similarly, an analysis of records from the Gene Expression Omnibus (GEO) dataset showed that CCL4 was upregulated in human osteosarcoma tissue. Importantly, the expression of both CCL4 and integrin αvß3 correlated positively with osteosarcoma clinical stages and lung metastasis. Analysis of osteosarcoma cell lines identified that CCL4 promotes integrin αvß3 expression and cell migration by activating the focal adhesion kinase (FAK), protein kinase B (AKT), and hypoxia inducible factor 1 subunit alpha (HIF-1α) signaling pathways, which can downregulate microRNA-3927-3p expression. Pharmacological inhibition of CCR5 by maraviroc (MVC) prevented increases in integrin αvß3 expression and cell migration. This study is the first to implicate CCL4 as a potential target in the treatment of metastatic osteosarcoma.

CCN2 promotes drug resistance in osteosarcoma by enhancing ABCG2 expression.

In recent years, osteosarcoma survival rates have failed to improve significantly with conventional treatment modalities because of the development of chemotherapeutic resistance. The human breast cancer resistance protein/ATP binding cassette subfamily G member 2 (BCRP/ABCG2), a member of the ATP-binding cassette family, uses ATP hydrolysis to expel xenobiotics and chemotherapeutics from cells. CCN family member 2 (CCN2) is a secreted protein that modulates the biological function of cancer cells, enhanced ABCG2 protein expression and activation in this study via the α6ß1 integrin receptor and increased osteosarcoma cell viability. CCN2 treatment downregulated miR-519d expression, which promoted ABCG2 expression. In a mouse xenograft model, knockdown of CCN2 expression increased the therapeutic effect of doxorubicin, which was reversed by ABCG2 overexpression. Our data show that CCN2 increases ABCG2 expression and promotes drug resistance through the α6ß1 integrin receptor, whereas CCN2 downregulates miR-519d. CCN2 inhibition may represent a new therapeutic concept in osteosarcoma.

Amphiregulin Promotes Vascular Endothelial Growth Factor-C Expression and Lymphangiogenesis through STAT3 Activation in Human Chondrosarcoma Cells.

BACKGROUND/AIMS: Chondrosarcoma is the second most common primary malignancy of bone, characterized by a high metastatic potential. Increasing clinical data highlight the important role played by lymphangiogenesis in cancer metastasis. Amphiregulin (AR) has been implicated in tumor metastasis and lymphangiogenesis, but its association with vascular endothelial growth factor-C (VEGF-C) expression and lymphangiogenesis in chondrosarcoma is unclear. METHODS: We used qPCR, ELISA and Western blotting to detect AR-induced VEGF-C expression in chondrosarcoma cells. Lymphangiogenesis was investigated by lymphatic endothelial cells (LECs) migration and tube formation. An in vivo experiment examined AR expression in tumor-associated lymphangiogenesis. RESULTS: In this study, we found that both AR and VEGF-C expression correlated with tumor stage and were significantly higher than levels found in normal cartilage. Exogenous AR promoted VEGF-C expression in chondrosarcoma cells in a time- and dose-dependent manner and subsequently increased migration and tube formation of LECs. AR also increased VEGF-C expression and lymphangiogenesis through the Src/MEK/ERK/STAT3 signaling pathway. However, it is unclear as to how an EGFR ligand (AR) induces activation of the Src kinase. Knockdown of AR decreased VEGF-C expression in chondrosarcoma cells. Similarly, lymphangiogenesis was abolished in AR knockdown cells in an in vivo model of chondrosarcoma. CONCLUSION: These results indicate that AR occurs through the Src/MEK/ERK/STAT-3 pathway, activating VEGF-C expression and contributing to lymphangiogenesis in human chondrosarcoma. Thus, AR could be a therapeutic target in metastasis and lymphangiogenesis of chondrosarcoma.

Variations in the AURKA Gene: Biomarkers for the Development and Progression of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a liver malignancy and a major cause of cancer mortality worldwide. AURKA (aurora kinase A) is a mitotic serine/threonine kinase that functions as an oncogene and plays a critical role in hepatocarcinogenesis. We report on the association between 4 single nucleotide polymorphisms (SNPs) of the AURKA gene (rs1047972, rs2273535, rs2064836, and rs6024836) and HCC susceptibility as well as clinical outcomes in 312 patients with HCC and in 624 cancer-free controls. We found that carriers of the TT allele of the variant rs1047972 were at greater risk of HCC compared with wild-type (CC) carriers. Moreover, carriers of at least one A allele in rs2273535 were less likely to progress to stage III/IV disease, develop large tumors or be classified into Child-Pugh class B or C. Individuals with at least one G allele at AURKA SNP rs2064863 were at lower risk of developing large tumors or progressing to Child-Pugh grade B or C. Our results indicate that genetic variations in the AURKA gene may serve as an important predictor of early-stage HCC and be a reliable biomarker for the development of HCC.

CTGF increases drug resistance to paclitaxel by upregulating survivin expression in human osteosarcoma cells.

Osteosarcoma is the most common primary malignant tumor, and its treatments require more effective therapeutic approaches. Paclitaxel has a broad range of antitumor activities, including apoptosis-inducing effects. However, the majority of tumors in patients with advanced cancer eventually develop chemoresistance. Connective tissue growth factor (CTGF) is a secreted protein that modulates the invasiveness of certain human cancer cells by binding to integrins. However, the effect of CTGF in paclitaxel-mediated chemotherapy is unknown. Here, we report that the expression of CTGF in osteosarcoma patients was significantly higher than that of the CTGF expression in normal bone tissues. Overexpression of CTGF increased the resistance to paclitaxel-mediated cell apoptosis. In contrast, knockdown of CTGF expression by CTGF shRNA increased the chemotherapeutic effect of paclitaxel. In addition, CTGF increased resistance to paclitaxel-induced apoptosis through upregulation of survivin expression. Moreover, the AMP-activated protein kinase (AMPK)-dependent nuclear factor kappa B (NF-κB) pathway mediated paclitaxel-increased chemoresistance and survivin expression. In a mouse xenograft model, overexpression of CTGF promoted resistance to paclitaxel. In contrast, knockdown of CTGF expression increased the therapeutic effect of paclitaxel in this model. In conclusion, our data indicate that CTGF might be a critical oncogene of human osteosarcoma involved in resistance to paclitaxel treatment.

The effect of low-level laser therapy on osteoclast differentiation: Clinical implications for tooth movement and bone density.

Background/purpose: Osteoclast differentiation is crucial for orchestrating both tooth movement and the maintenance of bone density. Therefore, the current study sought to explore the impact of low-level laser therapy (LLLT) on osteoclast differentiation, functional gene expression, molecular signaling pathways, and orthodontic tooth movement in clinical settings. Materials and methods: The RAW 264.7 cell line served as the precursor for osteoclasts, and these cells underwent irradiation using a 808-nm LLLT. Osteoclast differentiation was assessed through tartrate-resistant acid phosphatase (TRAP) staining. Functional gene expression levels were evaluated using real-time quantitative polymerase chain reaction (RT-qPCR) while signaling molecules were examined through Western blot analysis. In the clinical study, 12 participants were enrolled. Their tooth movement was monitored using a TRIOS desktop scanner. Bone density measurements were conducted using Mimics software, which processed cone-beam computed tomography (CBCT) images exported in Digital Imaging and Communications in Medicine (DICOM) format. Results: We found that LLLT effectively promoted receptor activator of nuclear factor-κB ligand (RANKL)-dependent osteoclast differentiation and the expression of osteoclast functional genes, including matrix metallopeptidase 9 (MMP9), nuclear factor of activated T-cells cytoplasmic 1(NFATc1), tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CTSK) in RAW264.7 cells. Clinically, the cumulative tooth movement over 90 days was significantly higher in the laser group than in the control group. Conclusion: Our research demonstrates that LLLT not only significantly promotes osteoclast differentiation but is also a valuable adjunct in orthodontic therapy.

Thrombin induces epidermal growth factor receptor transactivation and CCL2 expression in human osteoblasts.

OBJECTIVE: Thrombin is a key factor involved in the stimulation of fibrin deposition, angiogenesis, and proinflammatory processes. Abnormalities in these processes are primary features of rheumatoid arthritis (RA). The aim of this study was to investigate the intracellular signaling pathways involved in thrombin-induced CCL2 expression in human osteoblasts. METHODS: Thrombin-mediated CCL2 expression was assessed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The mechanisms of action of thrombin in different signaling pathways were studied using Western blotting. Knockdown of protease-activated receptor (PAR) protein was achieved by small interfering RNA (siRNA) transfection. Chromatin immunoprecipitation assays were used to study in vivo binding of c-Jun to the CCL2 promoter. Transient transfection was used to examine activator protein 1 (AP-1) activity. RESULTS: Stimulation of human primary osteoblasts and MG-63 cells with thrombin induced CCL2 expression. PAR-1-specific siRNA (but not other PAR siRNA) was involved in thrombin-mediated up-regulation of CCL2. Thrombin-mediated CCL2 production was attenuated by the thrombin inhibitor PPACK, the protein kinase Cδ (PKCδ) inhibitor rottlerin, the c-Src inhibitor PP2, epidermal growth factor receptor (EGFR) inhibitor AG-1478, MEK inhibitors PD98059 and U0126, or AP-1 inhibitors curcumin and tanshinone IIA. Stimulation of cells with thrombin increased PKCδ, c-Src, EGFR, MEK, and ERK activation. Treatment of osteoblasts with thrombin also increased c-Jun phosphorylation, AP-1 luciferase activity, and c-Jun binding to the AP-1 element on the CCL2 promoter. CONCLUSION: Our results suggest that the interaction between thrombin and PAR-1 increases CCL2 expression in human osteoblasts via the PKCδ/c-Src/ EGFR transactivation/MEK/ERK/c-Jun/AP-1 pathway.

Prediction of physiological state, cognition, sensory function, and biomarkers for frailty in patients aged 55 years or more with schizophrenia.

AIM: We explored the performance of demographic characteristics, physiological state, cognitive function, sensory function, and biomarkers when used as predictors of frailty for patients with schizophrenia. DESIGN: A cross-sectional study design was adopted. METHODS: Demographic data and data on physiological state, cognitive function, sensory function, biochemical indices, and frailty status of patients with schizophrenia were collected. The data were analysed using descriptive statistics, a chi-square test, one-factor analysis of variance, and logistic regression. RESULTS: The results revealed that frailty was prevalent among patients with lower educational attainment, longer hospital stay, higher skeletal muscle mass, higher basal metabolic rate, lower cognitive function, the use of tranquillisers and sleeping pills, and the use of assistive equipment as well as having fallen in the past year. In addition, cognitive function (p < 0.05), use of a wheelchair (p < 0.05), and use of an assistive walker (p < 0.001) were used as predictors of frailty condition of patients with schizophrenia. PATIENT CONTRIBUTION: Patients with schizophrenia have higher risk of having complications than patients with other chronic illnesses. Therefore, medical staff should regularly assess the levels of frailty risk to help patients with schizophrenia.

Chemokine Ligand 2 Promotes Migration in Osteosarcoma by Regulating the miR-3659/MMP-3 Axis.

Osteosarcoma is a common malignant tumor in children and adolescents, known for its aggressive invasion and distant metastasis, leading to a poor prognosis. Matrix metalloproteinases (MMPs) can degrade the extracellular matrix and basement membranes through their proteolytic activity, thereby promoting osteosarcoma metastasis. Chemokine ligand 2 (CCL2) is a well-studied chemokine that plays a significant role in the cell motility of many cancers. However, its specific involvement in osteosarcoma metastasis is not fully understood. The aim of this study is to examine the role of miRNAs in CCL2-mediated MMP expression and cell motility in human osteosarcoma. The analysis of immunohistochemistry data and databases associated a positive correlation between CCL2 or MMP-3 levels with the metastasis of osteosarcoma patients. The in vivo lung metastatic osteosarcoma model also demonstrated similar effects, showing higher levels of CCL2 and MMP-3 in lung metastatic osteosarcoma tissues. The stimulation of osteosarcoma cells with CCL2 enhanced migration and invasion abilities through the upregulation of MMP-3 synthesis. Our results also indicate that CCL2 enhances MMP-3-dependent cell motility by inhibiting miR-3659 synthesis. Therefore, CCL2 represents a promising therapeutic target for treating metastasis in osteosarcoma.

Apelin promotes osteosarcoma metastasis by upregulating PLOD2 expression via the Hippo signaling pathway and hsa_circ_0000004/miR-1303 axis.

Osteosarcoma is a highly mortal bone tumor, with a high metastatic potential, promoted in part by the enzyme procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2). Increasing level of PLOD2 in osteosarcoma tissue correlates with lymphatic and distant metastasis. The adipokine apelin (APLN) is also found in different cancers and APLN upregulation promotes angiogenesis and metastasis, but its effects on osteosarcoma metastasis are uncertain. We explored APLN functioning in metastatic osteosarcoma. An analysis of records from the Gene Expression Omnibus (GEO) database showed higher levels of APLN expression in osteosarcoma tissue than in normal tissue. Similarly, levels of APLN and PLOD2 mRNA synthesis were upregulated in osteosarcoma tissue. Levels of APLN and PLOD2 protein correlated positively with osteosarcoma clinical stages. APLN increased PLOD2 expression in human osteosarcoma cell lines and cell migration via the mammalian Sterile 20-like kinase 1 (MST1), monopolar spindle-one-binder protein (MOB)1, and YAP cascades, and through hsa_circ_0000004 functioning as a sponge of miR-1303. We also found that knockdown of APLN antagonized lung metastasis in mice with osteosarcoma. APLN may be a therapeutic target in osteosarcoma metastasis.

Bone sialoprotein promotes lung cancer osteolytic bone metastasis via MMP14-dependent mechanisms.

Bone metastases during lung cancer are common. Bone sialoprotein (BSP), a non-collagenous bone matrix protein, plays important functions in bone mineralization processes and in integrin-mediated cell-matrix interactions. Importantly, BSP induces bone metastasis in lung cancer, but the underlying mechanisms remain unclear. This study therefore sought to determine the intracellular signaling pathways responsible for BSP-induced migration and invasion of lung cancer cells to bone. Analyses of the Kaplan-Meier, TCGA, GEPIA and GENT2 databases revealed that high levels of BSP expression in lung tissue samples were associated with significantly decreased overall survival (hazard ratio = 1.17; p = 0.014) and with a more advanced clinical disease stage (F-value = 2.38, p < 0.05). We also observed that BSP-induced stimulation of matrix metalloproteinase (MMP)-14 promoted lung cancer cell migration and invasion via the PI3K/AKT/AP-1 signaling pathway. Notably, BSP promoted osteoclastogenesis in RAW 264.7 cells exposed to RANKL and BSP neutralizing antibody reduced osteoclast formation in conditioned medium (CM) from lung cancer cell lines. Finally, at 8 weeks after mice were injected with A549 cells or A549 BSP shRNA cells, the findings revealed that the knockdown of BSP expression significantly reduced metastasis to bone. These findings suggest that BSP signaling promotes lung bone metastasis via its direct downstream target gene MMP14, which reveals a novel potential therapeutic target for lung cancer bone metastases.

IOX-1 suppresses metastasis of osteosarcoma by upregulating histone H3 lysine trimethylation.

New therapeutic approaches are needed for metastatic osteosarcoma (OS), as survival rates remain low despite surgery and chemotherapy. Epigenetic changes, such as histone H3 methylation, play key roles in many cancers including OS, although the underlying mechanisms are not clear. In this study, human OS tissue and OS cell lines displayed lower levels of histone H3 lysine trimethylation compared with normal bone tissue and osteoblast cells. Treating OS cells with the histone lysine demethylase inhibitor 5-carboxy-8-hydroxyquinoline (IOX-1) dose-dependently increased histone H3 methylation and inhibited cellular migratory and invasive capabilities, suppressed matrix metalloproteinase expression, reversed epithelial-to-mesenchymal transition by increasing levels of epithelial markers E-cadherin and ZO-1 and decreasing the expression of mesenchymal markers N-cadherin, vimentin, and TWIST, and also reduced stemness properties. An analysis of cultivated MG63 cisplatin-resistant (MG63-CR) cells revealed lower histone H3 lysine trimethylation levels compared with levels in MG63 cells. Exposing MG63-CR cells to IOX-1 increased histone H3 trimethylation and ATP-binding cassette transporter expression, potentially sensitizing MG63-CR cells to cisplatin. In conclusion, our study suggests that histone H3 lysine trimethylation is associated with metastatic OS and that IOX-1 or other epigenetic modulators present promising strategies to inhibit metastatic OS progression.

The Relationship between Sarcopenia and Injury Events: A Systematic Review and Meta-Analysis of 98,754 Older Adults.

The main purpose of this study was to investigate the relationship between sarcopenia and injury events (falls, fractures, hospitalization, disability, and death). This study systemically searched the literature from Embase, PubMed, MEDLINE, CINAHL, and Cochrane Library and analyzed the collected literature using the random effects model to demonstrate the relationship between sarcopenia and injury events. This study followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and collected a total of 38 prospective studies, and the results showed that, when compared to robust individuals, the risk of injury events for older individuals with sarcopenia was significantly higher for fractures (HR = 9.66, CI: 5.07-18.38), hospital admissions (HR = 11.80, CI: 4.86-28.65), and death (HR = 9.57, CI: 3.17-28.94). In consideration of the negative impact of sarcopenia on the subsequent health of older adults, professional nursing personnel should assess older adults for sarcopenia as early as possible and propose relevant care policies to further reduce negative health impacts.

Muscle Strength, Physical Fitness, Balance, and Walking Ability at Risk of Fall for Prefrail Older People.

Aim: This study was to explore the relationship of older adults' demographic information, physiological indices, and stages of frailty with their risk of falling. Methods: In the cross-sectional study, a total of 221 older adults with the mean age 74.9 (SD = 6.8) years old were surveyed by senior fitness test. Results: Results were observed in terms of participants' physical fitness, with significant differences being observed in the correlations of left-hand grip strength (t = 5.05, p < .000), right-hand grip strength (t = 6.03, p < .000), and total grip strength (t = 5.70, p < .000), time up and go test (t = -6.25, p < .000), and 30-sec chair stand test (t = 7.19, p < .000) with the risk of falling. According to the logistic regression analysis results, long-term medication (OR = 0.12, 95% CI =0.02-0.62, p < .01) and right-hand grip strength (OR = 0.86, 95% CI =0.76-0.97, p < .01) are the main predictors of older adults' risk of falling. Conclusions: Older females with low education, history of falls, weaker grip strengths; taking longer to finish the TUG test; and standing fewer times during the 30-second chair stand test were at risk of fall. In prediction, older people using long-term medication were at lower risk of falling, and the greater the hand grip strength was, the lower the fall risk was. According to the research results, nursing personnel must develop care programs and improve older adults' risk of falls.

The Chemokine CCL4 Stimulates Angiopoietin-2 Expression and Angiogenesis via the MEK/ERK/STAT3 Pathway in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a common malignant tumor with a poor prognosis and is a major public health burden in Taiwan. Angiogenesis, the formation of new blood vessels, promotes tumor proliferation, maintenance, and metastasis. Angiopoietin 2 (Angpt2), a mitogen with a strong angiogenic effect, is highly specific to endothelial cells and a key player in angiogenesis. The inflammatory chemokine (C-C motif) ligand 4 (CCL4) is also important in the pathogenesis and progression of cancer. In this study, an analysis of records from The Cancer Genome Atlas (TCGA) database found higher CCL4 expression in oral cancer tissue than in normal healthy tissue. CCL4 treatment of oral cancer cells upregulated Angpt2 expression and stimulated mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase 1/2 (ERK), and signal transducer and activator of transcription 3 (STAT3) phosphorylation. Transfection of oral cancer cells with MEK, ERK, and STAT3 inhibitors and their small interfering RNAs inhibited CCL4-induced promotion of Angpt2 expression and angiogenesis. In a mouse model of OSCC, CCL4-treated cells promoted neovascularization in implanted Matrigel plugs, whereas inhibiting CCL4 expression suppressed Angpt2 expression and angiogenesis. CCL4 shows promise as a new molecular therapeutic target for inhibiting angiogenesis and metastasis in OSCC.