Association of Serum Potassium Variability With 60-day Mortality and Cardiovascular Events after COVID-19 Infection in Maintenance Hemodialysis Patients.

Objective: This study aimed to investigate the association between serum potassium variability and 60-day mortality and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients following the coronavirus disease 2019 (COVID-19) infection. Methods: We conducted a retrospective study on MHD patients treated at the affiliated hospital of Qingdao University hemodialysis center who were infected with the novel coronavirus between December 1, 2022, and January 31, 2023. Baseline characteristics of patients were collected from electronic medical records. Kaplan-Meier survival analysis was used to obtain patient survival probabilities, and multivariate Cox hazard regression models and binary Logistic regression models were used to obtain hazard ratios (HR), odds ratios (OR), and 95% confidence intervals (95% CI) between exposure and outcomes. Results: A total of 296 patients were included in this study, with a mean age of 57.2±16.3 years, and 59.8% were male. The 60-day mortality rate was 10.8%, and the incidence of CVD was 32.8%. Kaplan-Meier curves showed that a higher potassium variability coefficient was associated with higher all-cause mortality (P = 0.024). After adjusting for potential confounders, multivariate Cox regression analysis showed that the HR for 60-day mortality in the Q4 group compared to the Q1 group was 2.06 (95% CI = 1.03-4.09, P = 0.040), and binary Logistic regression analysis showed that the OR for 60-day CVD in the Q4 group compared to the Q1 group was 4.09 (95% CI = 1.52-10.97, P = 0.005). Conclusion: Increased serum potassium variability in MHD patients after COVID-19 infection significantly increased the likelihood of 60-day mortality and CVD.

Pleckstrin homology and RhoGEF domain containing G4 (PLEKHG4) leads to the activation of RhoGTPases promoting the malignant phenotypes of thyroid cancer.

Thyroid cancer (TC) is one of the most common endocrine system cancers, and its incidence is elevating. There is an urgent need to develop a deeper understanding of TC pathogenesis and explore new therapeutic target for its treatment. This study aimed to investigate the effects of pleckstrin homology and RhoGEF domain containing G4 (PLEKHG4) on the progression of TC. Herein, 29 pairs of TC and adjacent tissues were used to assess the expression of PLEKHG4. A xenograft model of mouse was established by subcutaneously injected with TC cells. Lung metastasis model was established through left ventricular injection. The results revealed that PLEKHG4 was up-regulated in human TC tissues. PLEKHG4 level was correlated with clinicopathological parameters of TC patients. In vitro assays revealed that PLEKHG4 promoted TC cell proliferation, migration, invasion, and epithelial-mesenchymal transformation. Knockdown of PLEKHG4 led to the opposite effects, and the loss of PLEKHG4 enhanced the apoptosis ability and inhibited the stemness properties of TC cells. These findings were further confirmed by the in vivo growth and lung metastasis of TC tumor. Mechanistically, PLEKHG4 promoted the activation of RhoGTPases RhoA, Cdc42, and Rac1. The inhibitors of these RhoGTPases reversed the PLEKHG4-induced malignant phenotypes. Additionally, ubiquitin-conjugating enzyme E2O (UBE2O), a large E2 ubiquitin-conjugating enzyme acted as an ubiquitin enzyme of PLEKHG4, facilitated its ubiquitination and degradation. In conclusion, PLEKHG4, regulated by UBE2O, promoted the thyroid cancer progression via activating the RhoGTPases pathway. UBE2O/PLEKHG4/RhoGTPases axis is expected to be a novel a therapeutic target for TC treatment.

Hypermethylation of microRNA-497-3p contributes to progression of thyroid cancer through activation of PAK1/ß-catenin.

MicroRNA-497 (miR-497) has been reported to be a tumor-suppressive miRNA in thyroid cancer (TC), yet the mechanism is not clearly defined. In this study, we aim to determine the mechanism by which miR-497-3p affects the progression of TC. After characterization of low miR-497-3p expression pattern in TC and normal tissues, we assessed the correlation between miR-497-3p expression and clinicopathological features of TC patients. Its low expression shared associations with advanced tumor stage and lymph node metastasis. ChIP and methylation-specific PCR provided data showing that downregulation of miR-497-3p in TC tissues was induced by DNA methyltransferase-mediated hypermethylation. By performing dual-luciferase reporter assay, we identified that miR-497-3p targeted PAK1 while PAK1 could inhibit ß-catenin expression. Through this mechanism, miR-497-3p exerted the anti-proliferative, anti-invasive, pro-apoptotic, and anti-tumorigenic effects on TC cells on the strength of the results from gain-of-function and rescue experiments. This study suggested that hypermethylation of miR-497-3p resulted in upregulation of ß-catenin dependent on PAK1 and contributed to cancer progression in TC, which highlighted one of miR-mediated tumorigenic mechanism.

Long non-coding ROR promotes the progression of papillary thyroid carcinoma through regulation of the TESC/ALDH1A1/TUBB3/PTEN axis.

Papillary thyroidal carcinoma (PTC) is a common endocrine cancer that plagues people across the world. The potential roles of long non-coding RNAs (lncRNAs) in PTC have gained increasing attention. In this study, we aimed to explore whether lncRNA ROR affects the progression of PTC, with the involvement of tescalcin (TESC)/aldehyde dehydrogenase isoform 1A1 (ALDH1A1)/ßIII-tubulin (TUBB3)/tensin homolog (PTEN) axis. PTC tumor and adjacent tissues were obtained, followed by measurement of lncRNA ROR and TESC, ALDH1A1, and TUBB3 expression. Interactions among lncRNA ROR, TESC, ALDH1A1, TUBB3, and PTEN were evaluated by ChIP assay, RT-qPCR, or western blot analysis. After ectopic expression and depletion experiments in PTC cells, MTT and colony formation assay, Transwell assay, and flow cytometry were performed to detect cell viability and colony formation, cell migration and invasion, and apoptosis, respectively. In addition, xenograft in nude mice was performed to test the effects of lncRNA ROR and PTEN on tumor growth in PTC in vivo. LncRNA ROR, TESC, ALDH1A1, and TUBB3 were highly expressed in PTC tissues and cells. Overexpression of lncRNA ROR activated TESC by inhibiting the G9a recruitment on the promoter of TESC and histone H3-lysine 9me methylation. Moreover, TESC upregulated ALDH1A1 expression to increase TUBB3 expression, which then reduced PTEN expression. Overexpression of lncRNA ROR, TESC, ALDH1A1 or TUBB3 and silencing of PTEN promoted PTC cell viability, colony formation, migration, and invasion while suppressing apoptosis. Moreover, overexpression of lncRNA ROR increased tumor growth by inhibiting PTEN in vivo. Taken together, the current study demonstrated that lncRNA ROR mediated TESC/ALDH1A1/TUBB3/PTEN axis, thereby facilitating the development of PTC.

Nitrogen and Fluorine Dual Doping of Soft Carbon Nanofibers as Advanced Anode for Potassium Ion Batteries.

Potassium-ion batteries (PIBs) are recognized as promising alternatives for lithium-ion batteries as the next-generation energy storage systems. However, the larger radius of K+ hinders the K+ insertion into the conventional carbon electrode and results in sluggish potassiation kinetics and poor cycling stability. Here, nitrogen and fluorine dual doping of soft carbon nanotubes (NFSC) anode are synthesized in one pot, achieving extraordinary electrochemical performance for PIBs. It is demonstrated that NFSC with a doping dose of 5.6 at% nitrogen and 1.3 at% fluorine together exhibits the highest reversible capacity of 238 mAh g-1 at 0.2 A g-1 and cycling stability of 186 mAh g-1 after 1000 cycles at 1 A g-1 . The extraordinary electrochemical performance can be attributed to the hollow structure, expanded interlayer distance, nitrogen and fluorine dual doping, and the binding ability of abundant defect sites. Moreover, density functional theory shows that the extra fluorine modification can dramatically enhance the conventional nitrogen doping effect and reduces the formation energy which makes a great contribution to the improvement of electrical conduction and K-ions insert. This work may promote the development of low-cost and sustainable carbon-based materials for PIBs and other advanced energy storage devices.

Plasma miR-323 as a Biomarker for Screening Papillary Thyroid Cancer From Healthy Controls.

The present study aims to evaluate whether plasma miR-323 serves as a potential biomarker to screen patients with papillary thyroid cancer (PTC) from healthy controls. Real-time PCR was performed to evaluate miR-323 expression in healthy controls and benign thyroid nodule (BTN) and PTC patients. Receiver operating characteristic (ROC) curve analysis was used to evaluate whether plasma miR-323 could be used to screen PTC patients from BTN patients and healthy controls. Plasma miR-323 was significantly increased in PTC patients compared with that in BNT patients and healthy controls. Moreover, miR-323 in the thyroid tissue was significantly increased in PTC patients when compared to BNT patients. We further showed that plasma and tissue miR-323 levels were significantly increased in PTC patients with metastasis compared to those without metastasis. Plasma miR-323 was significantly increased in PTC patients with BRAF V600E mutation when compared to those with wild-type BRAF. Furthermore, plasma miR-323 was significantly increased in PTC patients with higher Tg-FNAB. ROC analysis showed that plasma miR-323 could distinguish PTC patients from BNT patients and healthy controls. The present study demonstrated that plasma miR-323 might be an effective noninvasive indicator for PTC progression and serve as a biomarker for the diagnosis of PTC.

miR-744-5p mediates lncRNA HOTTIP to regulate the proliferation and apoptosis of papillary thyroid carcinoma cells.

Papillary thyroid carcinoma (PTC) is the most common malignancy in thyroid. miR-744-5p plays an efficient role in various cancers, but its role in PTC remains unknown. In this work, we aimed to explore the function of miR-744-5p and the mechanism by which miR-744-5p acted in PTC. We observed that miR-744-5p expression was significantly declined in PTC tissues and cell lines. The high level of miR-744-5p is significantly associated with a better clinical picture of PTC patients. Overexpression of miR-744-5p inhibited the proliferation, arrested the cell cycle, and promoted the apoptosis in PTC cells. Oppositely, down-regulation of miR-744-5p reversed the above tendencies. We also found that miR-744-5p down-regulated its downstream genes c-myc and attenuated cell proliferation induced by c-myc. Long non-coding RNA (lncRNA) HOTTIP was found to be up-regulated and to act as an oncogene in PTC. In this study, miR-744-5p bound to HOTTIP and was negatively regulated by HOTTIP. In conclusion, miR-744-5p acts as a tumor suppressor to inhibit proliferation and promotes the apoptosis of PTC cells via targeting c-myc. Moreover, miR-744-5p expression interferes with lncRNA HOTTIP ability to promote proliferation and downregulate apoptosis in papillary thyroid carcinoma.

Knockout of ASAP1 induces autophagy in papillary thyroid carcinoma by inhibiting the mTOR signaling pathway.

Due to lymph node metastasis and infiltration, surgery for PTC (papillary thyroid carcinoma) is a high-risk treatment strategy. Our work reports for the first time that ASAP1 (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1) is highly expressed in PTC and that its high expression is related to autophagy. Autophagy and ASAP1 expression in 40 PTC tissues and normal tissues were detected by immunofluorescence. We used the lentiviral CRISPR/Cas9 nickase to generate stable cell lines. The difference in autophagy levels between the ASAP1 KO group and the control group was determined by Western blot and immunofluorescence analyses. We added chloroquine (CQ) to verify that ASAP1 increased the formation of autophagosomes rather than reducing their degradation. The expression of mTOR activity-related proteins (P-P70S6K, P-MTOR) was studied by Western blotting. ASAP1 was upregulated while autophagy was downregulated in PTC tissues compared to normal tissues. Knockout of ASAP1 induced autophagy in both MDA-T32 and MDA-T85 cells. Knockout of ASAP1 attenuated the activation of the mTOR signaling pathway. Our studies demonstrated that ASAP1 is upregulated while autophagy is reduced in PTC tissues. In addition, knockout of ASAP1 induces autophagy in PTC by inhibiting the mTOR signaling pathway.

Polyphyllin I suppresses proliferation and promotes apoptosis of gastric cancer cell by inhibiting stat3 phosphorylation.

BACKGROUND: Polyphyllin I, a bioactive phytochemical extracted from Rhizoma Paridis, has been reported to exhibit anticancer activity. However, little is known about the potential of Polyphyllin I in induction of gastric cancer (GC) cell apoptosis and its underlying mechanisms. METHODS: Dual-luciferase reporter assay was performed to test the bioactivity of Polyphyllin I on inhibiting JAK2/STAT3 signaling pathway. The anti-proliferation activity of Polyphyllin I was tested using cell clone formation assay. The effect of Polyphyllin I on cell cycle and apoptosis were confirmed by flow cytometry and TUNEL assay. Western blot was used to test the effect of Polyphyllin I on JAK/STAT3 pathway and apoptosis related proteins. The subcutaneous GC mouse model was established to examine whether polyphyllin I could inhibit GC growth in vivo. RESULTS: A dual-luciferase reporter assay showed that polyphyllin I could inhibit the activity of Bcl-2 which is downstream of JAK2/STA3. Polyphyllin I significantly inhibited GC cell proliferation and induced cell apoptosis in a dose-dependent manner. The western blot results indicated that polyphyllin I mainly inhibited the phosphorylation of STAT3 by the way which is different from AG490. It was inferred that polyphyllin I may inhibit the JAK2/STAT3 pathway and affect the expression level of apoptosis related genes. Finally, in the tumor xenograft experiment proved that polyphyllin I significantly inhibited the growth of GC in vivo. CONCLUSIONS: Polyphyllin I may play its anticancer activity by inhibiting phosphorylation of STAT3 in GC cells.

Downregulation of MiR-431 expression associated with lymph node metastasis and promotes cell invasion in papillary thyroid carcinoma.

BACKGROUNDS: The purpose of this study was to investigate clinical role and functional effects of miR-431 expression in papillary thyroid carcinoma (PTC). METHODS: Expression of miR-431 in PTC patient tissue samples and plasma samples was examined by using qRT-PCR methods. Cell migration and invasion capacity were evaluated using transwell assays. Western blot analysis was performed to detect protein expression after miR-431 overexpression in PTC cells. RESULTS: We demonstrated that miR-431 expression was lower in PTC tissues and plasma samples compared to their corresponding controls. MiR-431 expression was particularly lower in PTC patients with lymph node (LN) metastasis. In vitro, miR-431 overexpression significantly inhibited cell migration, invasion and EMT process by upregulating E-cadherin and downregulating Vimentin expression. Additionally, wedemonstrated that miR-431 overexpression suppressed Hedgehog (Hh) signaling pathway by downregulating Gli1 expression. CONCLUSION: Our results indicated that miR-431 could serve as a predictor for PTC patients with positive lymph node metastasis and a potential target of PTC treatment.

LncRNA PTCSC3 affects drug resistance of anaplastic thyroid cancer through STAT3/INO80 pathway.

BACKGROUND: LncRNA PTCSC3 is a tumor suppressor in thyroid cancer, and its role in drug resistance of anaplastic thyroid cancer (ATC) to chemotherapy drug doxorubicin was investigated in this study. METHODS: Expression of RNA and protein was analyzed by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze the expression rate of CD133+ cells. The endogenous expression of related genes was modulated by recombinant plasmids and cell transfection. Combination condition and interaction between PTCSC3 and STAT3 were determined by RIP and RNA pull-down assay, respectively. MTT assay was performed to detect cytotoxicity. Chromatin immunoprecipitation was conducted to identify interactions between STAT3 and DNA promoter of INO80. RESULTS: LncRNA PTCSC3 was low-expressed in ATC tissues and cells. Over-expressed PTCSC3 inhibited the drug resistance of ATC to doxorubicin. PTCSC3 negatively regulated STAT3, and STAT3 promoted expression of INO80. PTCSC3 regulated INO80 through STAT3. PTCSC3 suppressed stem cells properties and drug resistance of ATC to doxorubicin. CONCLUSION: LncRNA PTCSC3 inhibits INO80 expression by negatively regulating STAT3, and thereby attenuating drug resistance of ATC to chemotherapy drug doxorubicin.

LncRNA HOTTIP promotes papillary thyroid carcinoma cell proliferation, invasion and migration by regulating miR-637.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Besides, increasing evidence has demonstrated that long non-coding RNA (lncRNA) HOTTIP played a crucial role in cancer pathogenesis. MiR-637-mediated Akt1 was involved in cell growth, invasion and migration in various malignancies. This study was aimed to investigate the potential biological effect and regulatory mechanism of HOTTIP on cell proliferation, invasion and migration in PTC. METHODS: Expression of HOTTIP, miR-637 and Akt1 were determined by quantitative RT-PCR (qRT-PCR) and western blotting in PTC tissues, normal tissues, PTC cells (TPC-1 and HTH83) or non-tumor thyroid cells (Nthy-ori 3-1). Cell proliferation, invasion and migration following HOTTIP knockdown were investigated in PTC cells. The target of HOTTIP was validated by RNA immunoprecipitation (RIP) and pull-down assay. Moreover, a xenograft model was performed. RESULTS: HOTTIP was upregulated in human PTC tissues and PTC cell lines. In addition, HOTTIP knockdown inhibited the proliferation, invasion and migration in vitro together with in vivo tumorigenesis of PTC cells. Additionally, HOTTIP knockdown downregulated Akt1 expression and suppressed cell proliferation, invasion and migration in PTC cells by regulating miR-637. In contrast, miR-637 inhibitor reversed above-mentioned tendencies caused by HOTTIP knockdown. CONCLUSION: HOTTIP is a potential oncogene in PTC and may serve as a therapeutic target for malignancies.

MicroRNA-21 regulates biological behaviors in papillary thyroid carcinoma by targeting programmed cell death 4.

BACKGROUND: Our recent study has found that microRNA-21 (miRNA-21) was significantly upregulated in papillary thyroid carcinoma (PTC) tissues compared with nontumor tissues by using miRNA microarray chip. However, the function of miRNA-21 is unknown in PTC. The aim of this study was to investigate the roles of miRNA-21 in PTC and the mechanism of gene regulation by it. METHODS: We transfected PTC cell line (TPC-1) with pEZX-eGFP-miRNA-21 plasmid to determine the biological functions of miRNA-21. Western blot assay was applied to investigate the correlation between miRNA-21 and programmed cell death 4 (PDCD4) expression in TPC-1 cell line. RESULTS: Overexpression of miRNA-21 could significantly enhance proliferation and invasion and inhibit the apoptosis of TPC-1 cells. In addition, miRNA-21 and PDCD4 expression showed a significantly negative correlation in TPC-1 cells. CONCLUSIONS: These data suggest that miRNA-21 may play an oncogenic role by directly targeting PDCD4 in the cellular processes of PTC. In addition, the findings in our present study also may represent new clues for the diagnostic and therapeutic strategies in the treatment of PTC.

Comparison of the effects of Mg-6Zn and Ti-3Al-2.5V alloys on TGF-ß/TNF-α/VEGF/b-FGF in the healing of the intestinal tract in vivo.

To evaluate the different effects of Mg-6Zn alloy and Ti-3Al-2.5V alloy implants in intestinal tract healing, we compared these two different alloys with respect to their effect on a rat's intestinal tract, using serum magnesium, radiology, pathology and immunohistochemistry in vivo. It was found using the scanning electron microscope that the Mg-6Zn alloy began to degrade during the first week and that the Ti-3Al-2.5V alloy was non-degradable throughout the process. The Mg-6Zn alloy did not have an impact on serum magnesium. Superior to the Ti-3Al-2.5V alloy, the Mg-6Zn alloy enhanced the expression of transforming growth factor-ß1 in healing tissue, and promoted the expression of both the vascular endothelial growth factor and the basic fibroblast growth factor, which helped angiogenesis and healing. The Mg-6Zn alloy reduced the expression of the tumor necrosis factor (TNF-α) at different stages and decreased inflammatory response, which may have been related to the zinc inhibiting TNF-α. In general, the Mg-6Zn alloy performed better than Ti-3Al-2.5V at promoting healing and reducing inflammation. The Mg-6Zn alloy may be a promising candidate for use in the pins of circular staplers for gastrointestinal reconstruction in medicine.

Comparison of the effects of Mg-6Zn and titanium on intestinal tract in vivo.

To evaluate the ability of Mg-6Zn to replace titanium nails in the reconstruction of the intestinal tract in general surgery, we compared the Mg-6Zn and titanium implants with respect to their effects on rat's intestinal tract by biochemical, radiological, pathological and immunohistochemical methods. The results indicated that Mg-6Zn implants started to degrade at the third week and disintegrate at the fourth week. No bubbles appeared, which may be associated with intestinal absorption of the Mg-6Zn implants. Pathological analyses (containing liver, kidney and cecum tissues) and biochemical measurements, including serum magnesium, creatinine, blood urea nitrogen, glutamic-pyruvic-transaminase and glutamic-oxaloacetic-transaminase proved that degradation of Mg-6Zn did not harm the important organs, which is an improvement over titanium implants. Immunohistochemical results showed that Mg-6Zn could enhance the expression of transforming growth factor-ß1. Mg-6Zn reduced the expression of tumor necrosis factor at different stages. In general, our study demonstrates that the Mg-6Zn alloy had good biocompatibility in vivo and performed better than titanium at promoting healing and reducing inflammation. It may be a promising candidate for stapler pins in intestinal reconstruction.