Expression and Functional Identification of SPL6/7/9 Genes under Drought Stress in Sugarbeet Seedlings.

Sugar beet is a significant sugar crop in China, primarily cultivated in arid regions of the north. However, drought often affects sugar beet cultivation, leading to reduced yield and quality. Therefore, understanding the impact of drought on sugar beets and studying their drought tolerance is crucial. Previous research has examined the role of SPL (SQUAMOSA promoter-binding protein-like) transcription factors in plant stress response; however, the precise contribution of SPLs to the drought stress response in sugar beets has yet to be elucidated. In this study, we identified and examined the BvSPL6, BvSPL7, and BvSPL9 genes in sugar beets, investigating their performance during the seedling stage under drought stress. We explored their drought resistance characteristics using bioinformatics, quantitative analysis, physiological experiments, and molecular biology experiments. Drought stress and rehydration treatments were applied to sugar beet seedlings, and the expression levels of BvSPL6, BvSPL7, and BvSPL9 genes in leaves were quantitatively analyzed at 11 different time points to evaluate sugar beets' response and tolerance to drought stress. Results indicated that the expression level of the BvSPL6/9 genes in leaves was upregulated during the mid-stage of drought stress and downregulated during the early and late stages. Additionally, the expression level of the BvSPL7 gene gradually increased with the duration of drought stress. Through analyzing changes in physiological indicators during different time periods of drought stress and rehydration treatment, we speculated that the regulation of BvSPL6/7/9 genes is associated with sugar beet drought resistance and their participation in drought stress response. Furthermore, we cloned the CDS sequences of BvSPL6, BvSPL7, and BvSPL9 genes from sugar beets and conducted sequence alignment with the database to validate the results. Subsequently, we constructed overexpression vectors, named 35S::BvSPL6, 35S::BvSPL7, and 35S::BvSPL9, and introduced them into sugar beets using Agrobacterium-mediated methods. Real-time fluorescence quantitative analysis revealed that the expression levels of BvSPL6/7/9 genes in transgenic sugar beets increased by 40% to 80%. The drought resistance of transgenic sugar beets was significantly enhanced compared with the control group.

PECAM-1 drives ß-catenin-mediated EndMT via internalization in colon cancer with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) is considered to be a risk factor in carcinogenesis and progression, although the biological mechanisms are not well understood. Here we demonstrate that platelet-endothelial cell adhesion molecule 1 (PECAM-1) internalization drives ß-catenin-mediated endothelial-mesenchymal transition (EndMT) to link DM to cancer. METHODS: The tumor microenvironment (TME) was investigated for differences between colon cancer with and without DM by mRNA-microarray analysis. The effect of DM on colon cancer was determined in clinical patients and animal models. Furthermore, EndMT, PECAM-1 and Akt/GSK-3ß/ß-catenin signaling were analyzed under high glucose (HG) and human colon cancer cell (HCCC) supernatant (SN) or coculture conditions by western and immunofluorescence tests. RESULTS: DM promoted the progression and EndMT occurrence of colon cancer (CC). Regarding the mechanism, DM induced PECAM-1 defection from the cytomembrane, internalization and subsequent accumulation around the cell nucleus in endothelial cells, which promoted ß-catenin entry into the nucleus, leading to EndMT occurrence in CC with DM. Additionally, Akt/GSK-3ß signaling was enhanced to inhibit the degradation of ß-catenin, which regulates the process of EndMT. CONCLUSIONS: PECAM-1 defects and/or internalization are key events for ß-catenin-mediated EndMT, which is significantly boosted by enhanced Akt/GSK-3ß signaling in the DM-associated TME. This contributes to the mechanism by which DM promotes the carcinogenesis and progression of CC. Video Abstract.

Peripheral immunophenotypes associated with the flare in the systemic lupus erythematosus patients with low disease activity state.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by clinical heterogeneity and flare unpredictability. It was still unclear for the association between SLE flare and immunophenotypes. Flow cytometric analysis defined the B and T subsets of the low disease activity state (LDAS) patients and healthy controls. Principal components analysis (PCA) and cluster analysis (CA) distinguished the immunophenotypes. Compared with the 66 healthy controls, the 93 LDAS patients had higher proportions of plasma cells, double negative B cells, naïve B cells and CD8+T cells, and lower proportions of unswitched memory B cells and CD4+T cells. PCA showed the abnormalities of T and B cell axes. CA divided the patients into 3 groups. The memory B cells group had the lower flare risk compared with the non-memory B cells group (including naïve B cells group and T cells group). The immunophenotypes were associated with SLE flare in the LDAS patients.

Alterations of peripheral blood B cell subsets in Chinese patients with adult idiopathic inflammatory myopathies.

OBJECTIVES: Abnormalities and hyperactivation of B cells have been described in idiopathic inflammatory myopathies (IIM). However, little is known about changes in the homeostasis of peripheral blood B cells in adult IIM patients. The aim of this study was to identify phenotypic alterations of B cell subsets and their relation to the overall clinical profile. METHODS: Blood samples were collected from 25 adult IIM patients and 15 healthy controls. Peripheral B cell subsets were classified into non-switched memory B cells (CD19+CD27+lgD+), switched memory B cells (CD19+CD27+lgD-), double-negative (DN) memory B cells (CD19+CD27-lgD-) and naïve B cells (CD19+CD27-lgD+) based on their surface phenotype as measured by flow cytometry. The clinical profile of IIM and its correlation with B cell subsets was further evaluated. RESULTS: Frequencies of CD19+ B cells and naïve B cells were increased in adult IIM patients compared with healthy controls (p=0.005 and p<0.001, respectively) and the frequency of memory B cells was decreased (p<0.001). Moreover, patients with a rash had lower non-switched memory B cells proportion (p=0.032). Patients with anti-MDA5+ antibodies had higher CD19+ B cells proportion than anti-ARS+ patients (p=0.046). Patients who were not receiving treatment had elevated levels of CD19+ B cells and naïve B cells along with reduced non-switched memory B cells compared with patients who were receiving treatment (p=0.021, p=0.036 and p=0.032, respectively). CONCLUSIONS: Our findings demonstrate abnormalities in the homeostasis of the B cell subsets present in adult IIM patients, characterised by expanded CD19+ B cells and naïve B cells but reduced memory B cells. Phenotypic abnormalities of B cell subsets are associated with the presence of a rash, with anti-MDA5 positivity and with treatment.

Uncoupled bone remodeling is characteristic of bone damage in premenopausal women with new-onset systemic lupus erythematosus.

OBJECTIVE: To investigate the mechanism underlying systemic lupus erythematosus (SLE)-related bone loss by evaluating the bone mineral density (BMD) and bone turnover markers (BTMs) in premenopausal patients with new-onset SLE without any treatment. METHODS: BMD and BTMs of 106 premenopausal patients with new-onset SLE and 64 gender-, age- and body mass index (BMI)-matched healthy controls were analyzed. BMD was determined using dual energy X-ray absorptiometry (DXA). Serum BTMs were measured. RESULTS: Hip and lumbar spine BMD in premenopausal patients with new-onset SLE was significantly decreased compared with healthy controls. Higher rate of osteoporosis was observed in new-onset SLE patients (25% vs. 1%). Moreover, uncoupled bone remodeling evidenced by an increase in bone resorption marker ß-CTX (685.9 ± 709.6 pg/mL vs. 395.4 ± 326.0 pg/mL, P < 0.05) and decrease in bone formation markers PINP (37.4 ± 33.0 ng/mL vs. 46.1 ± 20.9 ng/mL, P < 0.05) and OC (11.4 ± 9.8 ng/mL vs. 18.2 ± 8.6 ng/mL, P < 0.05) was observed in premenopausal patients with new-onset SLE compared with healthy controls. Univariate correlation analyses showed negative correlations between OC and SLE Disease Activity Index (SLEDAI), and positive correlations between ß-CTX and SLEDAI. SLE patients positive for dsDNA, nucleosome showed lower OC and higher ß-CTX. CONCLUSION: Premenopausal patients with new-onset SLE had decreased BMD and abnormal bone metabolism with increased ß-CTX and decreased OC and P1NP levels, indicating uncoupled bone remodeling in new-onset SLE patients. Disease activity and abnormal immunity, especially the amount of antibodies in SLE patients, were strongly associated with abnormality of bone metabolism.

Cav 1.3 damages the osteogenic differentiation in osteoporotic rats by negatively regulating Spred 2-mediated autophagy-induced cell senescence.

Cav 1.3 can affect the classical osteoclast differentiation pathway through calcium signalling pathway. Here, we performed cell transfection, real-time fluorescence quantitative PCR (qPCR), flow cytometry, SA-ß-Gal staining, Alizarin Red S staining, ALP activity test, immunofluorescence, Western blot and cell viability assay to analyse cell viability, cell cycle, osteogenesis differentiation and autophagy activities in vitro. Meanwhile, GST-pull down and CHIP experiments were conducted to explore the influence of Cav 1.3 and Sprouty-related EVH1 domain 2 (Spred 2) on bone marrow-derived mesenchymal stem cells (BMSCs). The results showed that OS lead to the decreased of bone mineral density and differentiation ability of BMSCs in rats. Cav 1.3 was up-regulated in OS rats. Overexpression of Cav 1.3 inhibited the activity of BMSCs, the expression of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN), as well as promoted the cell cycle arrest and senescence. Furthermore, the negative correlation between Cav 1.3 and Spred 2 was found through GST-pull down and CHIP. Overexpression of Spred 2 increased the expressions of microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1 of BMSCs, which ultimately promoted the cell activity of BMSCs and ALP, RUNX2, OCN expression. In conclusion, Cav 1.3 negatively regulates Spred 2-mediated autophagy and cell senescence, and damages the activity and osteogenic differentiation of BMSCs in OS rats.

Honokiol Restores Polymyxin Susceptibility to MCR-1-Positive Pathogens both In Vitro and In Vivo.

The emergence of the plasmid-mediated colistin resistance gene mcr-1 has led to serious multidrug-resistant (MDR) Enterobacteriaceae infections, which are a great threat to the clinic. This study aims to find an inhibitor of MCR-1 to reestablish the use of polymyxins against MDR Enterobacteriaceae infections. Here, we determined that the natural compound honokiol could enhance the efficacy of polymyxins against MDR Enterobacteriaceae infections by a checkerboard MIC assay, a time-kill assay, a combined disk test, Western blotting, molecular simulation dynamics, and mouse infection models. The MIC results indicated that honokiol can recover the sensitivity of polymyxins against MCR-1-positive Klebsiella pneumoniae and Escherichia coli (with a fractional inhibitory concentration index ranging from 0.09 ± 0.00 to 0.27 ± 0.06). Based on time-kill curve analysis, all of the tested bacteria were killed within 1 h following the combined therapy with honokiol and polymyxins. Molecular simulation dynamics results suggested that honokiol directly binds to the MCR-1 active region, reducing the biological activity of MCR-1. The combination of honokiol and polymyxins could increase the 40% protection rate and reduce the bacterial load on the thigh muscles of mice. Our study indicates that honokiol is a predominant natural compound whose combination therapy with polymyxins is very promising in future treatment options for MCR-1-positive Enterobacteriaceae infections.IMPORTANCE In the present study, honokiol could effectively inhibit the activity of MCR-1 and showed almost no cytotoxicity to MH-S cells. According to our results, the combination of honokiol and polymyxin had a clear synergistic effect against MCR-1-positive Enterobacteriaceae in vitro Combination therapy also showed a powerful therapeutic effect in vivo, which can significantly improve mouse livability, reduced the load of bacteria, and reduced pathological change. This combined therapy of small molecule compounds and antibiotics may not continue to induce new bacterial resistance, due to the fact that MCR-1 targeted by honokiol is not indispensable for the bacterial viability; on the other hand, it can reduce the dosage of combined antibiotics, and it is also a promising alternative therapy for the treatment of drug-resistant infections in the future.

Formononetin alleviates Streptococcus suis infection by targeting suilysin.

Streptococcus suis serotype 2 (SS2) has become a leading pathogen responsible for swine industry and human infections, causing enormous economic loss and triggering food safety risk. New and alternative strategies for combating this microorganism are urgently needed. Suilysin (SLY), a pore-forming toxins produced by SS2 has been revealed play critical role during its infection and could be an ideal target for combating this pathogen. Here, we found that formononetin (Form) inhibited the haemolytic activity of SLY without exerting growth pressure on SS2 or affecting the expression of SLY. At the cellular infection level, Form treatment diminished the cytotoxicity induced by SLY or SS2 and inflammatory response induced by SS2. In addition, the treatment with Form reduced bacterial burden in livers and spleens in SS2 infected mice. These data revealed that Form could attenuate the pathogenesis of SS2 both in vitro and in vivo by targeting SLY, suggesting that this compound could be used in combating S. suis infections.

Beneficial effects of estrogens in obstructive sleep apnea hypopnea syndrome.

Epidemiological studies showing the higher frequency of obstructive sleep apnea hypopnea syndrome in men, polycystic ovary syndrome (PCOS), and in post-menopausal women suggest the beneficial role of estrogen. These findings are well supported by the pre-clinical studies (ten research studies described in this review) showing that estrogen and phytoestrogens attenuate the deleterious effects of chronic intermittent hypoxia (obstructive apnea in animals) on the genioglossal muscles and on other organs (co-morbidities) in ovariectomized rodents. Moreover, clinical studies (four research studies described in this review) have also shown the beneficial role of estrogen therapy on the parameters of obstructive apnea in post-menopausal women. The beneficial effects of estrogen and phytoestrogens on obstructive sleep apnea and its co morbidities have been attributed to increase in thioredoxin, Nrf-2, activation of p38 MAP kinases, inhibition of vagal C fibers, and attenuation of HIF-1α. It is possible that estrogen-mediated activation of p38 MAP kinase may inhibit HIF-1α to attenuate lung inflammation, which may inhibit the activation of vagal C fibers to attenuate bronchoconstriction and prevent obstruction during sleep. Moreover, estrogen-mediated increase in thioredoxin and Nrf-2 may also contribute in increasing antioxidant defense and attenuating inflammation.

Cav1.3 is upregulated in osteoporosis rat model and promotes osteoclast differentiation from preosteoclast cell line RAW264.7.

BACKGROUND: Osteoporosis (OP) is a systemic osteopathy with increased bone fragility and increased risk of fracture. Osteoclasts (OC) are the key target cells in the treatment of osteoporosis. We aimed to research the role of L-type calcium channel protein Cav1.3 in OC differentiation in this study. METHODS: OP rat model was established to detect the expression level of Cav1.3. Tartrate-resistant acid phosphatase assay was used to measure the differentiation of osteoclast during receptor activator of nuclear factor κ-Β ligand (RANKL)-induced osteoclasts formation. The expression of bone differentiation-related proteins were detected by western blot analysis. RESULTS: Cav1.3 is upregulated in OP rats. Knockdown of Cav1.3 inhibits the differentiation of RAW264.7. Cav1.3 regulates the cell differentiation and bone resorption of RAW264.7 during RANKL-induced osteoclasts formation, which is accompanied by upregulation of CaMK II, p-CERB, AP-1, NFATC1, and NF-κB. CONCLUSION: Cav1.3 plays an important role in osteoporosis and the differentiation of osteoclast, which might be involved with the bone differentiation-related proteins.

Crocin Improves the Endothelial Function Regulated by Kca3.1 Through ERK and Akt Signaling Pathways.

BACKGROUND/AIMS: Based on the protective effect of crocin against cardiovascular diseases, we hypothesize that crocin could improve endothelial function through activating the eNOS(endothelial nitric oxide synthase) /NO pathway and/or the intermediate-conductance Ca2+-activated K+ channels (KCa3.1). METHODS: In this study, rat aortic rings were used to assess the regulatory effect of crocin on vascular tone and nitric oxide, prostacyclin, and KCa3.1, all endothelial vasodilators, were analyzed for effects by crocin. The expression profiles of p-eNOS, total-eNOS, p-ERK, total-ERK, p-Akt, total-Akt, KCa3.1, CD31, thrombomodulin, ICAM-1 and VCAM-1 were tested by western blotting. KCa3.1 was also analyzed by qPCR and immunofluorescence staining. Fluorescence and confocal microscopy were used to determine NO generation and intracellular Ca2+. Both EdU and MTT assays were used to evaluate cell viability. Cellular migration was assessed using transwell assay. RESULTS: Crocin relaxed pre-contracted artery rings through either NO or KCa3.1, but not PGI, in an endothelium-dependent manner. Furthermore, crocin increased p-eNOS, total-eNOS expression and NO production as well as intracellular Ca2+ in both HUVECs and HUAECs (Human Umbilical Artery Endothelial cells). Crocin also stimulated the expression of CD31, thrombomodulin and vascular cell adhesion molecule 1 (VCAM-1), as well as increased cellular proliferation and migration in vitro. Interestingly, we determined for the first time that by blocking or silencing KCa3.1 there was inhibition of crocin induced upregulation of p-eNOS and total-eNOS. Correspondingly, the KCa3.1 inhibitor TRAM-34 also reduced the expression of CD31, thrombomodulin and VCAM-1, as well as diminished intracellular Ca2+, cellular proliferation and migration. Finally, crocin stimulated the expression of p-ERK, total-ERK, p-Akt and total-Akt, however suppression of MEK and Akt inhibited this expression profile in endothelial cells. CONCLUSION: In the present study, these data strongly support the hypothesis that crocin could improve endothelial function through stimulation of the eNOS/NO pathway and other endothelial markers. This functional improvement is regulated by KCa3.1 via the MEK/ERK and PI3K/Akt signaling pathway.

Role of Natural Killer T (NKT) Cells in Type II Diabetes-Induced Vascular Injuries.

BACKGROUND This study investigated the distribution and features of natural killer T (NKT) cells in the peripheral blood of diabetic patients, and their regulatory roles on vascular endothelial cells. MATERIAL AND METHODS Peripheral lymphocytes were isolated from diabetic patients. NKT cell distribution, proportion, and surface and intracellular markers were detected with flow cytometry. Peripheral blood-derived NKT cells were isolated and co-cultured with human umbilical vein endothelial cells (HUVECs). Proliferation and migration of HUVECs were assessed with the CCK-8 assay and the Transwell chamber assay. RESULTS The ratios of CD3-CD56+ NK and CD3+CD56+ NKT cells in the peripheral blood of patients with type II diabetes were significantly elevated. The expression levels of NKp30, NKG2D, and NKp44 on the surface were increased in the CD3+CD56+ NKT cells, while the expression levels of NKG2A and 158b were significantly downregulated. The expression level of granzymes in the peripheral blood-derived NKT cells were not changed in patients with type II diabetes, but the expression levels of IFNg and IL-4 were significantly increased. However, after co-culture with NKT cells derived from the peripheral blood of diabetic patients, the proliferation and migration of HUVECs were significantly inhibited, and was restored by treatment with IL-4 antibody. In addition, the IL-4 stimulus inhibited the proliferation and migration of HUVECs. ls were not changed in patients with type II diabetes, while the expression levels of IFNγ and IL-4 were significantly increased. However, after co-cultured with NKT cells derived from the peripheral blood of diabetic patients, the proliferation and migration of HUVECs were significantly inhibited, which could significantly restored by the treatment of IL-4 antibody. In addition, the IL-4 stimulus could down-regulate the proliferation and migration of HUVECs.  CONCLUSIONS Peripheral blood NKT cells are increased and activated in diabetes. NKT cells inhibit the proliferation and migration of HUVECs by secreting IL-4, thereby inducing vascular injuries.

Effect of 1,25-(OH)2D3 on Proliferation of Fibroblast-Like Synoviocytes and Expressions of Pro-Inflammatory Cytokines through Regulating MicroRNA-22 in a Rat Model of Rheumatoid Arthritis.

OBJECTIVE: This study aims to investigate the regulatory mechanism of 1,25-(OH)2D3 on the proliferation of fibroblast-like synoviocytes (FLS) and expressions of pro-inflammatory cytokines in rheumatoid arthritis (RA) rats via microRNA-22 (miR-22). METHODS: A rat model of RA was established with a subcutaneous injection of type II collagen. After treated with different concentrations of 1,25-(OH)2D3 the proliferation of FLS was estimated by the MTT method, and the optimal concentration of 1,25-(OH)2D3 was selected for further experiments. Cell proliferation was detected by MTT. Cell cycle and apoptosis were analyzed by FCM. The IL-1ß, IL-6, IL-8, and PGE2 protein expressions were determined by ELISA, and MMP-3, INOS, and Cox-2 mRNA expressions were measured by qRT-PCR. RESULTS: The rat model of RA was successfully established. Compared with the blank group, the 1,25-(OH)2D3 and miR-22 inhibitors groups exhibited higher proliferation inhibition and apoptosis rates, lower levels of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, and PGE2), and decreased mRNA expressions of MMP-3, INOS, and Cox-2. The miR-22 mimics group had lower proliferation inhibition and apoptosis rates, elevated expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 than the blank group. In contrast to the 1,25-(OH)2D3 group, the proliferation inhibition and apoptosis rates were down-regulated, and the expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 were up-regulated in the 1,25-(OH)2D3 + miR-22 mimics group. CONCLUSION: Our study demonstrated that 1,25-(OH)2D3 inhibits the proliferation of FLS and alleviates inflammatory response in RA rats by down-regulating miR-22.

SCARA5 plays a critical role in the progression and metastasis of breast cancer by inactivating the ERK1/2, STAT3, and AKT signaling pathways.

Scavenger receptor class A member 5 (SCARA5) is a candidate anti-oncogene in several malignancies. However, whether SCARA5 is a suppressor gene in breast cancer and its role in breast cancer cell growth and metastasis remain to be determined. Here, we investigated the biological functions of SCARA5 in the progression and metastasis of breast cancer and explored the underlying mechanisms. A total of 65 breast cancer patients and three cell lines (ZR-75-30, MCF-7, and MDA-MB-231) were analyzed in the study. RT-qPCR, western blotting, and immunohistochemistry were used to detect mRNA and protein expression, and lymphatic vessel density (LVD) and microvessel density (MVD). MTT, colony formation, TUNEL assays, invasion assays and Transwell assays, and flow cytometric analyses were used to evaluate the effect of SCARA5 on breast cancer cells. SCARA5 was significantly downregulated in breast cancer tissues and cells and significantly correlated with tumor size, histological grade, lymph node metastasis, pTNM stage, VEGF-A, VEGF-C, LVD, and MVD. SCARA5 overexpression significantly suppressed cell proliferation, colony formation, invasion, and migration, and induced G0/G1 arrest and apoptosis of ZR-75-30 cells. SCARA5 decreased the phosphorylation of ERK1/2, AKT, and STAT3, and downregulated downstream signaling effectors, including MMP-2, 3, and 9, VEGF-A, VEGF-C, Bax, Cyclin B1, Cyclin D1, and Cyclin E1, and upregulated E-cadherin, Bcl-2, and caspase 3. SCARA5 is associated with multiple signaling pathways and plays a critical role in the progression and metastasis of breast cancer. The present results provide the first evidence that SCARA5 inhibits lymphangiogenesis by downregulating VEGF-C, thereby inhibiting breast cancer lymphatic metastasis.

piR-55490 inhibits the growth of lung carcinoma by suppressing mTOR signaling.

Lung carcinoma is the most common human cancer with poor prognosis and has an increasing incidence in recent years. However, the related mechanism of lung cancer onset has not been completely explored. Piwi-interacting RNA (piRNA) is a type of noncoding small RNA with established function in germ cells, and interestingly, piRNA has also been shown to be implicated in cancer biology. In this study, piR-55490 was found to be silenced in lung carcinoma specimens and cell lines, compared with normal lung tissues and cells. Intriguingly, the expression level of piR-55490 is negatively associated with patients' survival. Restoration of piR-55490 can reduce the proliferation rates of lung cancer cells, while piR-55490 suppression led to the gain in the proliferation rates. Animal model study showed that piR-55490 can suppress the growth of lung carcinoma xenograft. Further study revealed that piR-55490 suppressed the activation of Akt/mTOR pathway in lung cancer cells. Surprisingly, piR-55490 was found to bind 3'UTR of mTOR messenger RNA (mRNA) and induce its degradation in a mechanism similar to microRNA (miRNA). The introduction of an mTOR construct resistant to action of piR-55490 was able to abolish the effect of piR-55490 on lung cancer cells. In conclusions, we found that piRNA can contribute to the suppression of cancer cell phenotypes by directly targeting a oncogene mRNA. This finding facilitates our understanding of piRNA's function and its association with human cancer.

Subclinical hypothyroidism and the risk of metabolic syndrome: A meta-analysis of observational studies.

BACKGROUND: Observational studies on the association between subclinical hypothyroidism (SCH) and metabolic syndrome (MetS) have produced inconsistent results. Therefore, we performed a meta-analysis to evaluate the effect of SCH on the risk of MetS. METHODS: Multiple databases were searched to identify studies on the association between SCH and the risk of MetS, up to February 2015. Relevant information for analysis was extracted. A random-effects model was used to calculate the pooled risk estimates. RESULTS: 9 studies (7 cross-sectional and 2 case-control studies) were included. The pooled odds ratio (OR) for MetS comparing SCH with euthyroid subjects was 1.31 (95%CI: 1.08 to 1.60, p = 0.006, I(2) = 50%). Subgroup analyses by countries revealed a significant association for the studies from Asian (OR = 1.244, 95% CI: 1.030-1.503, I(2) = 25%) other than non-Asian (OR = 1.548, 95% CI: 0.925-2.591, I(2) = 73.5%) countries. A positive association was identified in the IDF subgroup (OR = 1.288, 95% CI: 1.055-1.572, I(2) = 0%), but not in the NCEP-ATP III (OR = 1.351, 95% CI: 0.950-1.923, I(2) = 66.4%), Chinese (OR = 1.430, 95% CI: 0.891-2.294) and Japanese (OR = 1.542, 95% CI: 0.594-4.005, I(2) = 78.3%) subgroup. A certain degree of heterogeneity was observed among studies which cannot be explained by study design, diagnostic criteria and location. CONCLUSION: Our results demonstrated that SCH was significantly associated with a higher risk of MetS. Well-designed cohort studies were warranted to confirm our findings.

Roles of osteopontin and matrix metalloproteinase-7 in occurrence, progression, and prognosis of nonsmall cell lung cancer.

BACKGROUND: This study detected osteopontin (OPN) and matrix metalloproteinase-7 (MMP-7) expressions to explore the roles of OPN and MMP-7 in the occurrence, progression, and prognosis of nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: A retrospective study was conducted on NSCLC tissues (n = 152; case group) and adjacent nonneoplastic lung parenchyma (adjacent to tumor >5 cm; n = 152; control group) collected from 152 NSCLC patients. The protein expressions of OPN and MMP-7 were detected by immunohistochemistry. OPN and MMP-7 messenger RNA (mRNA) expressions were detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The protein and mRNA expressions of OPN and MMP-7 in NSCLC tissues were evidently higher than those in adjacent nonneoplastic lung parenchyma (all P < 0.05). OPN protein and mRNA expression were associated with the degree of differentiation, tumor node metastasis (TNM) staging, and lymph node metastasis in NSCLC (all P < 0.05). MMP-7 protein expression was associated with TNM staging and lymph node metastasis (both P < 0.05) while MMP-7 mRNA expression was associated with the degree of differentiation, TNM staging, and lymph node metastasis (all P < 0.05). A significantly positive relativity was revealed between OPN expression and MMP-7 expression (protein: r = 0.789, P < 0.001; mRNA: r = 0.377, P < 0.001). Lymph node metastasis, TNM staging, OPN, and MMP-7 protein expressions were independent risk factors for the prognosis of NSCLC (all P < 0.05). CONCLUSION: High MMP-7 and OPN protein expressions are closely related to the occurrence, progression, and prognosis of NSCLC, and can be served as unfavorable prognostic factors for NSCLC.

In emergency situations, tracheal intubation replaces fiberoptic bronchoscopy to extract foreign bodies from the airway, a case report.

Introduction: Foreign bodies in the airways can cause significant morbidity and mortality. If emergency personnel are unable to clear an airway obstruction frequently results in cardiac arrest. Patient concerns: A 78-year-old man developed a persistent cough and dyspnoea after consuming alcohol. Fiberoptic bronchoscopy was performed, revealing complete blockage of the main airways on both sides by fish. Diagnosis: Endotracheal foreign body. Interventions: The foreign body was removed with an endotracheal tube under the guidance of a fiberoptic bronchoscope. Outcomes: The airway foreign body had been successfully removed and the man recovered uneventfully. Conclusion: When repeated attempts to extract airway foreign bodies under the guidance of bronchoscopy have failed, endotracheal intubation can be considered as a viable alternative in emergency situations.

JAK inhibitors attenuate hyperactivation of nonswitched memory B cells in rheumatoid arthritis patients in remission.

OBJECTIVE: To investigate the distribution and activation of B-cell subpopulations in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis) and to analyze their correlation with disease remission. METHODS: Peripheral blood samples were collected from 23 adult healthy controls and 58 RA patients, 31 of whom were treated with JAKis and assessed during a 24-month follow-up. The number of peripheral B-cell subpopulations (including naive B cells, nonswitched memory B (NSMB) cells, switched memory B cells, and double-negative B cells), their activation, and phosphorylation of SYK and AKT upon B-cell receptor (BCR) stimulation in each population were analyzed by flow cytometry. RESULTS: Compared with that in healthy controls, the frequency of NSMB cells was significantly lower in new-onset untreated RA patients. However, expression of CD40, CD80, CD95, CD21low and pAKT significantly increased in these NSMB cells. Additionally, the number of NSMB cells correlated negatively with DAS28-ESR and IgG and IgA levels in these patients; expression of CD80, CD95 and CD21low on NSMB cells correlated positively with DAS28-ESR and IgG and IgA levels. After treatment with JAKis, the serum IgG concentration significantly decreased in RA patients in remission, but CD40, CD95 and pAKT levels in NSMB cells significantly decreased. CONCLUSION: RA patients present different B-cell subpopulations, in which the frequency of NSMB cells is negatively associated with disease activity. However, treatment with JAKis can inhibit activation of NSMB cells, restore the balance of kinase phosphorylation, and facilitate disease remission in RA patients.

Investigating the Effects of AL049796.1 Silencing in Inhibiting High Glucose-Induced Colorectal Cancer Progression.

Patients with colorectal cancer (CRC) and diabetes share many risk factors. Despite a strong association between diabetes and CRC being widely studied and confirmed, further genetic research is needed. This study found higher AL049796.1 and TEA domain transcription factor 1 (TEAD1) levels (both mRNA and protein) in CRC tissues of diabetic patients compared with nondiabetics, but no significant difference in miR-200b-3p levels. A positive correlation between AL049796.1 and TEAD1 protein existed regardless of diabetes status, whereas miR-200b-3p was only negatively correlated with TEAD1 protein in nondiabetic CRC tissues. In vitro experiments have shown that high glucose (HG) treatment increased AL049796.1 in CRC cells, and AL049796.1 silencing reduced HG-induced proliferation, migration and invasion, as well as connective tissue growth factor, cysteine-rich angiogenic inducer 61, and epidermal growth factor receptor protein expression. Mechanistic investigations indicated that AL049796.1 could mitigate suppression of miR-200b-3p on TEAD1 posttranscriptionally by acting as a competitive binder. In vivo, subcutaneous CRC tumors in streptozotocin (STZ)-induced mice grew significantly faster; AL049796.1 silencing did not affect the growth of subcutaneous CRC tumors but significantly reduced that of STZ-induced mice. Our study suggests that AL049796.1 independently contributes to the risk of CRC in diabetic patients, highlighting its potential as both a therapeutic target and a novel biomarker for CRC among individuals with diabetes.