The effect of childhood family adversity on adulthood depression among Chinese older migrant workers: gender differences in the mediating role of social-ecological systems.

BACKGROUND: Older migrant workers (OMWs) in China face unique challenges rooted in their early life experiences, which increase their vulnerability to psychological and behavioral problems in adulthood. By utilizing the cumulative disadvantage model and the social-ecological systems theory, this study explored the effect of childhood family adversity on adulthood depression in the mediating roles of OMWs' social-ecological microsystem and mesosystem and further examined gender differences in these associations. METHODS: Data were collected from the China Health and Retirement Longitudinal Study (CHARLS), involving a sample of 4,309 OMWs aged 50 and above. The measures included the Center for Epidemiological Research Depression Scale, childhood family adversity, socioeconomic status, marital quality, and physical and cognitive health. RESULTS: Childhood family adversity was positively associated with adulthood depression among OMWs. Social microsystem (physical and cognitive health) and mesosystem (marital quality and socioeconomic status) factors significantly mediated this relationship. Multi-group analysis revealed that the mediating effects of marital quality and socioeconomic status were stronger for female OMWs, while the mediating effects of physical and cognitive health were stronger for male OMWs. CONCLUSIONS: The findings suggest that childhood family adversity has a lasting impact on the mental health of OMWs, and that social-ecological systems factors play an important role in this relationship. The study also highlights the need for gender-specific interventions to address the mental health needs of OMWs.

Exploring the bi-directional relationship between periodontitis and dyslipidemia: a comprehensive systematic review and meta-analysis.

AIM: As periodontitis and dyslipidemia are diseases that occur with high incidence, the relationship between them has attracted much attention. Previous studies on these diseases have tended to focus on lipid parameters and periodontitis, we aimed to investigate the relationship between dyslipidemia and periodontitis. MATERIALS AND METHODS: A comprehensive search to identify the studies investigating the relationship between dyslipidemia and periodontitis was performed on PubMed, Web of Science and Cochrane Library before the date of August, 2023. Studies were considered eligible if they contained data on abnormal blood lipid parameters and periodontitis. Studies that reported mean differences and 95% confidence intervals or odds ratios were used. RESULTS: A total of 73 publications were included in the meta-analysis. Hyper total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) and lower high-density lipoprotein (HDL) levels are risk factors for periodontitis. Periodontal disease is a risk factor for high TG and low HDL levels. Three months after periodontal treatment, the levels of TC, TG and HDL were significantly improved, and statin treatment only improved gingival index (GI) levels compared to that of the dietary control. CONCLUSIONS: The findings reported here suggest that the mutual promotion of periodontitis and dyslipidemia can be confirmed. Non-surgical periodontal therapy may improve lipid abnormalities. It can't be demonstrated whether systematic application of statins have a better effect on the improvement in periodontal status in patients with dyslipidemia compared to that of the control.

Isorhamnetin as a novel inhibitor of pneumolysin against Streptococcus pneumoniae infection in vivo/in vitro.

The increasing incidence of Streptococcus pneumoniae (S. pneumoniae) infection severely threatened the global public heath, causing a significant fatality in immunocompromised hosts. Notably, pneumolysin (PLY) as a pore-forming cytolysin plays a crucial role in the pathogenesis of pneumococcal pneumonia and lung injury. In this study, a natural flavonoid isorhamnetin was identified as a PLY inhibition to suppress PLY-induced hemolysis by engaging the predicted residues and attenuate cytolysin PLY-mediated A549 cells injury. Underlying mechanisms revealed that PLY inhibitor isorhamnetin further contributed to decrease the formation of bacterial biofilms without affecting the expression of PLY. In vivo S. pneumoniae infection confirmed that the pathological injury of lung tissue evoked by S. pneumoniae was ameliorated by isorhamnetin treatment. Collectively, these results presented that isorhamnetin could inhibit the biological activity of PLY, thus reducing the pathogenicity of S. pneumoniae. In summary, our study laid a foundation for the feasible anti-virulence strategy targeting PLY, and provided a promising PLY inhibitor for the treatment of S. pneumoniae infection.

Anlotinib reduces the suppressive capacity of monocytic myeloid-derived suppressor cells and potentiates the immune microenvironment normalization window in a mouse lung cancer model.

By exploring the effects of an antiangiogenic small molecule drug named anlotinib on the levels of myeloid-derived suppressor cells (MDSCs) in a mouse xenograft model of lung cancer, the role of anti-angiogenesis in remodeling the immune microenvironment was discussed. In addition, the impact of anlotinib on the normalization of the immune microenvironment and time window was examined, providing a theoretical basis for the optimization of clinical strategies applying anlotinib combined with PD-1 inhibitors. On the basis of the LLC mouse xenograft model, MDSCs and MDSCs + immune microenvironment were examined in tissues, respectively, according to different samples. The former observation included the control (group A) and anlotinib monotherapy (group B) groups; the latter also included the control (group C) and anlotinib monotherapy (group D) groups. The levels of MDSCs in peripheral blood at different time points were analyzed by flow cytometry, and the levels of MDSCs in tissue samples at different time points were evaluated by immunofluorescence and immunohistochemistry. The volumes of subcutaneous xenografts were significantly smaller in the anlotinib treatment group compared with the control group ( P < 0.005). Flow cytometry showed that compared with the control group, the intratumoral percentages of total MDSCs ( P < 0.01) and mononuclear-MDSCs ( P < 0.05) were significantly decreased on days 3 and 17 after anlotinib treatment in peripheral blood samples; however, there was no significant difference in granulocytic-MDSCs changes between the experimental and control groups. Immunofluorescence showed that the levels of MDSCs in both the experimental and control groups reached the lowest points 10 days after drug administration, and were significantly lower in the experimental group than in the control group ( P < 0.05). Anlotinib reduces the levels of MDSCs in the mouse xenograft model of lung cancer, with the characteristics of time window. This study provides a basis for further exploring strategies for anti-angiogenic treatment combined with immunotherapy in lung cancer based on time-window dosing.

NADPH oxidase 4 contributes to TRPV4-mediated endothelium-dependent vasodilation in human arterioles by regulating protein phosphorylation of TRPV4 channels.

Impaired endothelium-dependent vasodilation has been suggested to be a key component of coronary microvascular dysfunction (CMD). A better understanding of endothelial pathways involved in vasodilation in human arterioles may provide new insight into the mechanisms of CMD. The goal of this study is to investigate the role of TRPV4, NOX4, and their interaction in human arterioles and examine the underlying mechanisms. Arterioles were freshly isolated from adipose and heart tissues obtained from 71 patients without coronary artery disease, and vascular reactivity was studied by videomicroscopy. In human adipose arterioles (HAA), ACh-induced dilation was significantly reduced by TRPV4 inhibitor HC067047 and by NOX 1/4 inhibitor GKT137831, but GKT137831 did not further affect the dilation in the presence of TRPV4 inhibitors. GKT137831 also inhibited TRPV4 agonist GSK1016790A-induced dilation in HAA and human coronary arterioles (HCA). NOX4 transcripts and proteins were detected in endothelial cells of HAA and HCA. Using fura-2 imaging, GKT137831 significantly reduced GSK1016790A-induced Ca2+ influx in the primary culture of endothelial cells and TRPV4-WT-overexpressing human coronary artery endothelial cells (HCAEC). However, GKT137831 did not affect TRPV4-mediated Ca2+ influx in non-phosphorylatable TRPV4-S823A/S824A-overexpressing HCAEC. In addition, treatment of HCAEC with GKT137831 decreased the phosphorylation level of Ser824 in TRPV4. Finally, proximity ligation assay (PLA) revealed co-localization of NOX4 and TRPV4 proteins. In conclusion, both TRPV4 and NOX4 contribute to ACh-induced dilation in human arterioles from patients without coronary artery disease. NOX4 increases TRPV4 phosphorylation in endothelial cells, which in turn enhances TRPV4-mediated Ca2+ entry and subsequent endothelium-dependent dilation in human arterioles.

Dysfunctional role of elevated TIGIT expression on T cells in oral squamous cell carcinoma patients.

OBJECTIVE: This study was aimed to analyze the role of T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT) expression on T cells in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TILs) were collected from OSCC patients. The correlation between TIGIT expression and clinicopathologic features was analyzed by chi-square test. Phenotypic and functional study of TIGIT+ T cells were performed by flow cytometry. RESULTS: TIGIT was highly expressed on T cells from PBMC and TILs. High expression of TIGIT on CD4+ T cells (19.0%) and CD8+ T cells (35.9%) was also associated with higher T stage and nodal invasion. Moreover, TIGIT+ CD4+ and TIGIT+ CD8+ T cells sorted from OSCC patients showed a dysfunctional phenotype (low cell proliferation and low secretion of IL-2, TNF-α and IFN-γ), and TIGIT+ CD4+ T cells exhibited inhibitory function (high expression of Foxp3 and high amounts of IL-10). Importantly, TIGIT blockade can enhance the proliferation ability and effective cytokine production (IL-2, TNF-α, and IFN-γ) of CD4+ and CD8+ T cells from OSCC patients in vitro. CONCLUSIONS: TIGIT-expressing T cells exhibit a lower effector cytokine-releasing phenotype in OSCC patients.

Junction plakoglobin, a potential prognostic marker of oral squamous cell carcinoma, promotes proliferation, migration and invasion.

BACKGROUND: Junction plakoglobin (JUP) is an important cell-cell junction protein. Recently, its deregulation has been correlated with the initiation and progression of various malignancies. Our aim was to investigate the expression of JUP in oral squamous cell carcinoma (OSCC) and its correlation with prognosis and to further study the effects of JUP on the proliferation, apoptosis, migration and invasion of OSCC cells. METHODS: We detected JUP expression in 273 OSCC specimens using immunohistochemistry. We assessed the correlation of JUP expression with clinicopathologic parameters and patient survival by Cox regression. Then, expression levels of JUP in normal oral keratinocytes (NOKs) and OSCC cell lines were detected by Western blotting and quantitative real-time PCR (qPCR). Next, we used HSC3 cells to study the effect of JUP on tumor cell proliferation, apoptosis, migration, and invasion by using cell counting kit-8, flow cytometry, and transwell assays, respectively. RESULTS: Cox regression showed that high expression of JUP was related to the poor prognosis of OSCC patients. Western blotting and qPCR assays showed that the expression level of JUP in OSCC cell lines was higher than that in NOKs. Overexpression of JUP promoted the proliferation, metastasis, and invasion of HSC3 cells and inhibited apoptosis, while the opposite was observed after JUP knockdown. CONCLUSION: This study initially revealed that JUP was overexpressed in OSCC, and that JUP promoted the proliferation, migration, and invasion of OSCC cells and inhibited apoptosis. Moreover, high expression of JUP could be used as a potential prognostic marker of OSCC.

Downregulation of Cypher induces apoptosis in cardiomyocytes via Akt/p38 MAPK signaling pathway.

Background: Dilated cardiomyopathy (DCM) is considered as the most common form of non-ischemic cardiomyopathy with a high mortality worldwide. Cytoskeleton protein Cypher plays an important role in maintaining cardiac function. Genetic studies in human and animal models revealed that Cypher is involved in the development of DCM. However, the underlying molecular mechanism is not fully understood. Accumulating evidences suggest that apoptosis in myocytes may contribute to DCM. Thus, the purpose of this study is to define whether lack of Cypher in cardiomyocytes can elevate apoptosis signaling and lead to DCM eventually. Methods and Results: Cypher-siRNA sufficiently inhibited Cypher expression in cardiomyocytes. TUNEL-positive cardiomyocytes were increased in both Cypher knockdown neonatal rat cardiomyocytes and Cypher knockout mice hearts, which were rare in the control group. Flow cytometry further confirmed that downregulation of Cypher significantly increased myocytes apoptosis in vitro. Cell counting kit-8 assay revealed that Cypher knockdown in H9c2 cells significantly reduced cell viability. Cypher knockdown was found to increase cleaved caspase-3 expression and suppress p21, ratio of bcl-2 to Bax. Cypher-deficiency induced apoptosis was linked to downregulation of Akt activation and elevated p-p38 MAPK accumulation. Pharmacological activation of Akt with SC79 attenuated apoptosis with enhanced phosphorylation of Akt and reduced p-p38 MAPK and Bax expression. Conclusions: Downregulation of Cypher participates in the promotion of cardiomyocytes apoptosis through inhibiting Akt dependent pathway and enhancing p38 MAPK phosphorylation. These findings may provide a new potential therapeutic strategy for the treatment of DCM.

Identification, Pathogenicity, and Fungicide Sensitivity of Ascochyta caulina (Teleomorph: Neocamarosporium calvescens) Associated with Black Stem on Quinoa in China.

Quinoa black stem is a new disease that affects the stems of quinoa plants and is more likely to develop under cool conditions (15 to 25°C, RH = 55 ± 2%). The typical symptoms include the formation of black necrotic lesions on the stem, which can completely wrap around the stem, causing lodging and blanking (development of 'empty' and sterile grain on the panicle). Furthermore, the pycnidia form small round protrusions on the surface of the lesions. Phylogenetic analysis revealed that representative isolates LMHS-3 and LMHS-5 were closely related to Ascochyta caulina (teleomorph: Neocamarosporium calvescens). Comprehensive morphological and molecular characterizations confirmed A. caulina as the pathogen that caused quinoa black stem. A. caulina mainly infected quinoa stems and could produce many pycnidia, but it rarely infected quinoa leaves. Pathogenicity testing showed that the most suitable temperature for the onset of quinoa black stem was from 15 to 25°C. When the temperature was increased above 30°C, the conidial germination of A. caulina became malformed, and when the temperature was decreased below 5°C, mycelium growth of A. caulina became extremely slow; thus, both extreme high and low temperatures affected the pathogenicity of A. caulina. Mancozeb and azoxystrobin fungicides were revealed to have had the strongest inhibitory effects on the conidial germination of A. caulina, and in some cases caused malformations in conidial germination. Tebuconazole and difenoconazole had the strongest inhibitory effects on A. caulina mycelial growth and less on the effects on the conidial germination. The results of the present study provide a basis for the recognition and management of quinoa black stem.

An Intelligent Data Uploading Selection Mechanism for Offloading Uplink Traffic of Cellular Networks.

Wi-Fi uploading is considered an effective method for offloading the traffic of cellular networks generated by the data uploading process of mobile crowd sensing applications. However, previously proposed Wi-Fi uploading schemes mainly focus on optimizing one performance objective: the offloaded cellular traffic or the reduced uploading cost. In this paper, we propose an Intelligent Data Uploading Selection Mechanism (IDUSM) to realize a trade-off between the offloaded traffic of cellular networks and participants' uploading cost considering the differences among participants' data plans and direct and indirect opportunistic transmissions. The mechanism first helps the source participant choose an appropriate data uploading manner based on the proposed probability prediction model, and then optimizes its performance objective for the chosen data uploading manner. In IDUSM, our proposed probability prediction model precisely predicts a participant's mobility from spatial and temporal aspects, and we decrease data redundancy produced in the Wi-Fi offloading process to reduce waste of participants' limited resources (e.g., storage, battery). Simulation results show that the offloading efficiency of our proposed IDUSM is (56.54×10-7), and the value is the highest among the other three Wi-Fi offloading mechanisms. Meanwhile, the offloading ratio and uploading cost of IDUSM are respectively 52.1% and (6.79×103). Compared with other three Wi-Fi offloading mechanisms, it realized a trade-off between the offloading ratio and the uploading cost.

An Efficient Resource Allocation Strategy for Edge-Computing Based Environmental Monitoring System.

The cloud computing and microsensor technology has greatly changed environmental monitoring, but it is difficult for cloud-computing based monitoring system to meet the computation demand of smaller monitoring granularity and increasing monitoring applications. As a novel computing paradigm, edge computing deals with this problem by deploying resource on edge network. However, the particularity of environmental monitoring applications is ignored by most previous studies. In this paper, we proposed a resource allocation algorithm and a task scheduling strategy to reduce the average completion latency of environmental monitoring application, when considering the characteristic of environmental monitoring system and dependency among task. Simulations are conducted, and the results show that compared with the traditional algorithms. With considering the emergency task, the proposed methods decrease the average completion latency by 21.6% in the best scenario.

[Research advance of ANRIL on atherosclerosis by regulating cell proliferation and apoptosis].

Atherosclerosis is an important pathological basis for coronary artery disease. ANRIL is an antisense non-coding RNA located in Chr9p21 locus, which was identified as the most significant risk locus associated with atherosclerosis. ANRIL can produce multiple transcripts including linear and circular transcripts after various transcript splicing. It has been illustrated that ANRIL plays important roles in the pathology of atherosclerosis by regulating the proliferation and apoptosis of vascular cells. Linear ANRIL can regulate the proliferation of vascular smooth muscle cells (VSMCs) in plaques by chromatin modification, as well as influence the proliferation and the apoptosis of macrophages in post transcription; circular ANRIL can affect the proliferation and apoptosis of VSMCs by chromatin modification as well as interfering with rRNA maturation. In this review, we describe the ANRIL evolution, different transcripts characteristics, and their roles in the proliferation and apoptosis of vascular cells to participate in the process of atherosclerosis, for further understanding the pathogenesis of atherosclerosis and finding potential targets for diagnosis and treatment of atherosclerosis.

Novel polymorphisms in PDLIM3 and PDLIM5 gene encoding Z-line proteins increase risk of idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (IDCM), characterized by ventricular dilation and impaired systolic function, is a primary cardiomyopathy resulting in heart failure. During heart contraction, the Z-line is responsible for transmitting force between sarcomeres and is also a hot spot for muscle cell signalling. Mutations in Z-line proteins have been linked to cardiomyopathies in both humans and mice. Actinin-associated LIM protein (ALP) and enigma homolog protein (ENH), encoded by PDLIM3 and PDLIM5, are components of the muscle cytoskeleton and localize to the Z-line. A PDLIM3 or PDLIM5 deficiency in mice leads to dilated cardiomyopathy. Since PDLIM3 and PDLIM5 are candidate IDCM susceptibility genes, the current study aims to investigate whether polymorphisms within PDLIM3 and PDLIM5 could be correlated with IDCM. We designed a case-control study, and exons of the PDLIM3 and PDLIM5 were amplified by polymerase chain reactions in 111 IDCM patients and 137 healthy controls. We found that five synonymous polymorphisms had statistical distribution differences between IDCM patients and controls, including rs4861669, rs4862543, c.731 + 131 T > G, c.1789-3 C > T and rs7690296, according to genotype and allele distribution. Haplotype G-C-C-C and A-T-C-T (rs2306705, rs10866276, rs12644280 and rs4635850 synthesized) were regarded as risk factors for IDCM patients when compared with carriers of other haplotypes (all P < .05). Furthermore, IDCM patients with two novel polymorphisms (c.731 + 131 T > G and c.1789-3 C > T) had lower systolic blood pressure. In conclusion, these five synonymous polymorphisms might constitute a genetic background that increases the risk of the development of IDCM in the Chinese Han population.

Transient receptor potential vanilloid 4 (TRPV4) activation by arachidonic acid requires protein kinase A-mediated phosphorylation.

Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable channel of the transient receptor potential (TRP) superfamily activated by diverse stimuli, including warm temperature, mechanical forces, and lipid mediators such as arachidonic acid (AA) and its metabolites. This activation is tightly regulated by protein phosphorylation carried out by various serine/threonine or tyrosine kinases. It remains poorly understood how phosphorylation differentially regulates TRPV4 activation in response to different stimuli. We investigated how TRPV4 activation by AA, an important signaling process in the dilation of coronary arterioles, is affected by protein kinase A (PKA)-mediated phosphorylation at Ser-824. Wildtype and mutant TRPV4 channels were expressed in human coronary artery endothelial cells (HCAECs). AA-induced TRPV4 activation was blunted in the S824A mutant but was enhanced in the phosphomimetic S824E mutant, whereas the channel activation by the synthetic agonist GSK1016790A was not affected. The low level of basal phosphorylation at Ser-824 was robustly increased by the redox signaling molecule hydrogen peroxide (H2O2). The H2O2-induced phosphorylation was accompanied by an enhanced channel activation by AA, and this enhanced response was largely abolished by PKA inhibition or S824A mutation. We further identified a potential structural context dependence of Ser-824 phosphorylation-mediated TRPV4 regulation involving an interplay between AA binding and the possible phosphorylation-induced rearrangements of the C-terminal helix bearing Ser-824. These results provide insight into how phosphorylation specifically regulates TRPV4 activation. Redox-mediated TRPV4 phosphorylation may contribute to pathologies associated with enhanced TRPV4 activity in endothelial and other systems.

Mesenchymal stem cells participate in oral mucosa carcinogenesis by regulating T cell proliferation.

Recent evidences suggested that Mesenchymal stem cells (MSCs) may be involved in tumor formation by modulating of the tumor microenvironment, but it is still unclear the potential of MSCs in the malignant transformation of oral mucosa. Using a chemically-induced oral carcinogenesis model by 4-nitroquinoline-1-oxide (4NQO), we generated precancerous lesions and cancerous lesions in the oral cavity of rats. Flow cytometric analysis on lesions derived single cell suspension revealed an increase in the proportion of MSCs and a decreased proportion of T cell during oral mucosa malignancy. Moreover, MSCs showed increased immunosuppression capacity on T cell proliferation during mucosa malignancy. At last, we demonstrated that higher frequency of lesions resident MSCs was correlated with more Ki67 expression in the lesion, which indicated higher cellular proliferative status in the lesions. Our study demonstrated that MSCs may play an important role in oral mucosa malignant transformation through regulating T cell proliferation.

Multiscale experimental study on the effects of different weight-bearing levels during moderate treadmill exercise on bone quality in growing female rats.

BACKGROUND: Bone tissue displays a hierarchical organization. Mechanical environments influence bone mass and structure. This study aimed to explore the effects of different mechanical stimuli on growing bone properties at macro-micro-nano scales. METHODS: Sixty five-week-old female Wistar rats were treadmill exercised at moderate intensity with the speed of 12 m/min, and then randomly divided into five groups according to weight-bearing level. After 8 weeks of experiment, femurs were harvested to perform multiscale tests. RESULTS: Bone formation was significantly increased by weight-bearing exercise, whereas bone resorption was not significantly inhibited. Trabecular and cortical bone mineral densities showed no significant increase by weight-bearing exercise. The microstructure of trabecular bone was significantly improved by 12% weight-bearing exercise. However, similar positive effects were not observed with further increase in weight-bearing levels. The nanomechanical properties of trabecular bone were not significantly changed by weight-bearing exercise. The macrostrength of whole femur and the nanomechanical properties of cortical bone significantly decreased in the 19% and 26% weight-bearing exercise groups. CONCLUSION: When rats ran on the treadmill at moderate intensity during growth period, additional 12% weight-bearing level could significantly increase bone formation, improve microstructure of trabecular bone, as well as maintain the structure and mechanical properties of cortical bone. Excessive weight-bearing level caused no positive effects on the trabecular bone microstructure and properties of cortical bone at all scales. In addition, increased weight-bearing level exerted no significant influence on trabecular and cortical bone mineral densities.

Thrombomodulin (TM) in tumor cell differentiation and periphery blood immune microenvironment in oral squamous cell carcinoma.

Thrombomodulin (TM, also known as CD141), which functions as an anticoagulant, is widely expressed on cell surface of a variety of cell types, including human blood cells as well as certain immune cells. To determine whether TM could be a potential marker for OSCC diagnosis as well as a molecular target for OSCC therapy, we examined the expression of TM in an oral cancer tissue microarray with 153 oral cancer tissues. Further, we also analyzed the expression of TM on DCs of 36 OSCC patients and 36 healthy donors. The expression of TM was determined using standard immunohistochemistry on a tissue microarray of 153 OSCC patients. Flow cytometric analyses were performed to determine the proportions of CD141+ DCs in the PBMC of 36 OSCC patients and 36 healthy donors. Clinicopathological correlations were performed based on the available clinical data. Our results showed that in the univariate analysis, high TM expression was significantly associated with well differentiation of tumor cells (P=.001), but not correlated with overall survival and disease-free survival (P>.05). In addition, CD141+ DCs were both present in OSCC patients and healthy donors with about 0.04%. There was no significant difference with the percentages of CD141+ DCs in the PBMC of OSCC patients and that of the normal control group (P>.05). This study indicates that TM expression might play the most critical role in the differentiation of OSCC tumors. Functional distinctions of CD141+ DCs in OSCC patients deserve further investigation to provide important therapeutic understandings for future immunotherapy.

Multiscale investigation on the effects of additional weight bearing in combination with low-magnitude high-frequency vibration on bone quality of growing female rats.

This study aimed to explore the effects of additional weight bearing in combination with low-magnitude high-frequency vibration (LMHFV; 45 Hz, 0.3 g) on bone quality. One hundred twenty rats were randomly divided into ten groups; namely, sedentary (SED), additional weight bearing in which the rat wears a backpack whose weight is x% of the body weight (WBx; x = 5, 12, 19, 26), basic vibration (V), and additional weight bearing in combination with LMHFV in which the rat wears a backpack whose weight is x% of the body weight (Vx; x = 5, 12, 19, 26). The experiment was conducted for 12 weeks, 7 days per week, and 15 min per day. A three-point bending mechanical test, micro computed tomography, and a nanoindentation test were used. Serum samples were analyzed chemically. Failure load in V19 rats was significantly lower than that in SED rats (P < 0.05). Vx (x = 5, 12, 19, 26) rats showed poor microarchitectures. The content of tartrate-resistant acid phosphatase 5b was significantly higher in Vx (x = 5, 12, 19, 26) rats than that in SED rats (P < 0.05). V26 rats demonstrated comparatively better nanomechanical properties of materials than the other vibrational groups. Additional weight bearing in combination with LMHFV negatively affected the macromechanical properties and microarchitecture of bone. Heavy additional weight bearing, such as 26% of body weight, in combination with LMHFV was able to improve the nanomechanical properties of growing bone material compared with LMHFV. A combined mechanical stimulation was used, which may provide useful information to understand the mechanism of this mechanical stimulation on bone.

Current status and strategies of long noncoding RNA research for diabetic cardiomyopathy.

Long noncoding RNAs (lncRNAs) are endogenous RNA transcripts longer than 200 nucleotides which regulate epigenetically the expression of genes but do not have protein-coding potential. They are emerging as potential key regulators of diabetes mellitus and a variety of cardiovascular diseases. Diabetic cardiomyopathy (DCM) refers to diabetes mellitus-elicited structural and functional abnormalities of the myocardium, beyond that caused by ischemia or hypertension. The purpose of this review was to summarize current status of lncRNA research for DCM and discuss the challenges and possible strategies of lncRNA research for DCM. A systemic search was performed using PubMed and Google Scholar databases. Major conference proceedings of diabetes mellitus and cardiovascular disease occurring between January, 2014 to August, 2018 were also searched to identify unpublished studies that may be potentially eligible. The pathogenesis of DCM involves elevated oxidative stress, myocardial inflammation, apoptosis, and autophagy due to metabolic disturbances. Thousands of lncRNAs are aberrantly regulated in DCM. Manipulating the expression of specific lncRNAs, such as H19, metastasis-associated lung adenocarcinoma transcript 1, and myocardial infarction-associated transcript, with genetic approaches regulates potently oxidative stress, myocardial inflammation, apoptosis, and autophagy and ameliorates DCM in experimental animals. The detail data regarding the regulation and function of individual lncRNAs in DCM are limited. However, lncRNAs have been considered as potential diagnostic and therapeutic targets for DCM. Overexpression of protective lncRNAs and knockdown of detrimental lncRNAs in the heart are crucial for defining the role and function of lncRNAs of interest in DCM, however, they are technically challenging due to the length, short life, and location of lncRNAs. Gene delivery vectors can provide exogenous sources of cardioprotective lncRNAs to ameliorate DCM, and CRISPR-Cas9 genome editing technology may be used to knockdown specific lncRNAs in DCM. In summary, current data indicate that LncRNAs are a vital regulator of DCM and act as the promising diagnostic and therapeutic targets for DCM.