Comprehensive transcriptomic analysis of immune-related genes in diabetic foot ulcers: New insights into mechanisms and therapeutic targets.

Background: Diabetic foot ulcers (DFU), affecting a quarter of diabetic patients and leading to high rates of amputation and mortality, pose significant health and economic burdens. Wound healing in DFU is often compromised by chronic inflammation, underscoring the critical role of immune cells. However, the systematic investigation of immune-related genes (IRGs) in DFU pathogenesis remains elusive.

Gynura divaricata (L.) DC. promotes diabetic wound healing by activating Nrf2 signaling in diabetic rats.

The Ethnopharmacological Significance: Diabetic chronic foot ulcers pose a significant therapeutic challenge as a result of the oxidative stress caused by hyperglycemia. Which impairs angiogenesis and delays wound healing, potentially leading to amputation. Gynura divaricata (L.

Bortezomib inhibits ZIKV/DENV by interfering with viral polyprotein cleavage via the ERAD pathway.

Flaviviruses have posed a serious threat to human health in the past decades, and effective therapeutic drugs are lacking; thus, treatment of flavivirus infection is a great challenge. The flavivirus protease NS2B3 is an attractive target for antiviral drug screening. Here, we developed an intracellular Zika virus (ZIKV) NS2AB3 self-cleavage assay to identify inhibitors that interfere with viral polyprotein cleavage and block ZIKV/dengue virus (DENV) replication.

Electrostatic Interaction Between NS1 and Negatively Charged Lipids Contributes to Flavivirus Replication Organelles Formation.

Flavivirus replication occurs in membranous replication compartments, also known as replication organelles (ROs) derived from the host ER membrane. Our previous study showed that the non-structural (NS) protein 1 (NS1) is the essential factor for RO creation by hydrophobic insertion into the ER membrane. Here, we found that the association of NS1 with the membrane can be facilitated by the electrostatic interaction between NS1 and negatively charged lipids.

Zika NS1-induced ER remodeling is essential for viral replication.

Zika virus (ZIKV), a recently emerged member of the flavivirus family, forms replication compartments at the ER during its lifecycle. The proteins that are responsible for the biogenesis of replication compartments are not well defined. Here, we show that Zika nonstructural protein 1 (NS1)-induced ER remodeling is essential for viral replication.

Zika NS2B is a crucial factor recruiting NS3 to the ER and activating its protease activity.

Zika virus (ZIKV) is an emergent flavivirus associated with severe neurological disorders. ZIKV NS3 protein is a viral protease that cleaves the ZIKV polyprotein precursor into individual viral proteins. In this study, we found that ZIKV NS3 by itself exhibited mitochondrial localization, which was quite different from its endoplasmic reticulum (ER) localization in ZIKV-infected cells.

Zika virus NS3 is a canonical RNA helicase stimulated by NS5 RNA polymerase.

Zika virus is a positive single-strand RNA virus whose replication involved RNA unwinding and synthesis. ZIKV NS3 contains a helicase domain, but its enzymatic activity is not fully characterized. Here, we established a dsRNA unwinding assay based on the FRET effect to study the helicase activity of ZIKV NS3, which provided kinetic information in real time.

Maltol, a food flavor enhancer, attenuates diabetic peripheral neuropathy in streptozotocin-induced diabetic rats.

Scope: Maltol (3-hydroxy-2-methy-4-pyrone), a potent antioxidative agent, typically is used to enhance flavor and preserve food. This study evaluated its effects on preventing diabetic peripheral neuropathy (DPN) in streptozotocin (STZ)-induced diabetic rats and explored its mechanisms.

Methods And Results: We intraperitoneally injected Sprague-Dawley (SD) rats with STZ (65 mg kg-1, ip) and treated the rats with different doses of maltol after 4 weeks of injection.

Vesicular stomatitis virus G protein transmembrane region is crucial for the hemi-fusion to full fusion transition.

Viral fusion proteins are essential for enveloped virus infection. These proteins mediate fusion between the virus envelope and host cellular membrane to release the viral genome into cells. Vesicular stomatitis virus G (VSV G) protein is a typical type III viral fusion protein.

Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells.

Glutaminolysis is important for metabolism and biosynthesis of cancer cells, and GLS is essential in the process. Selenite is widely regarded as a chemopreventive agent against cancer risk. Emerging evidence suggests that it also has chemotherapeutic potential in various cancer types, but the mechanism remains elusive.

Selenite-induced autophagy antagonizes apoptosis in colorectal cancer cells in vitro and in vivo.

In the present study, we aimed to investigate the relationship between autophagy and apoptosis in selenite‑treated colorectal cancer (CRC) cells. The effects of selenite on HCT116 and SW480 cell apoptosis were investigated with an Annexin V/propidium iodide (PI) double staining kit by flow cytometry. The punctate of LC3 protein following treatment with selenite was observed by a laser scanning confocal microscope and by transmission electron microscopy.

The switch from ER stress-induced apoptosis to autophagy via ROS-mediated JNK/p62 signals: A survival mechanism in methotrexate-resistant choriocarcinoma cells.

Background: Human choriocarcinoma, a highly curable solid tumour, is exceptionally sensitive to methotrexate-based chemotherapy at the metastatic stage. The present study aimed to investigate the molecular basis for this resistance to methotrexate therapy occurs in some cases, and these patients subsequently die from progressive and advanced disease.

Methods: The autophagy and apoptotic activity regulated by PERK/ATF4 axis in methotrexate-resistant JEG-3 and parental cells were evaluated with western blotting and chromatin immunoprecipitation (ChIP).

The p38 MAPK-regulated PKD1/CREB/Bcl-2 pathway contributes to selenite-induced colorectal cancer cell apoptosis in vitro and in vivo.

Supranutritional selenite has anti-cancer therapeutic effects in vivo; however, the detailed mechanisms underlying these effects are not clearly understood. Further studies would broaden our understanding of the anti-cancer effects of this compound and provide a theoretical basis for its clinical application. In this study, we primarily found that selenite exposure inhibited phosphorylation of cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), leading to suppression of Bcl-2 in HCT116 and SW480 colorectal cancer (CRC) cells.

WITHDRAWN: Selenite induces apoptosis in colorectal cancer cells through interaction with thioredoxin reductase.

Ahead of Print article withdrawn by publisher. The chemopreventive and chemotherapeutic effects of selenium compounds has been well validated in colorectal cancer by epidemiologic and pre-clinical studies, but the underlying mechanisms still remains elusive. We provide evidence that interaction between selenium metabolites and selenoproteins participates in colorectal cancer suppression induced by selenite.

ATF4 activation by the p38MAPK-eIF4E axis mediates apoptosis and autophagy induced by selenite in Jurkat cells.

Previous studies have shown that selenite exerts pro-apoptosis and pro-autophagy effects and is associated with the activation of ER stress in T-cell acute lymphoblastic leukemia (T-ALL). Herein we demonstrate the underlying mechanisms by which the activation of p38MAPK plays essential roles in apoptosis and autophagy and the coordination of cellular metabolic processes during leukemia therapy. MKK3/6-dependent activation of p38MAPK is required for the phosphorylation of eIF4E, thus initiating the translation of ER stress-related transcription factor ATF4.

Sodium selenite alters microtubule assembly and induces apoptosis in vitro and in vivo.

Background: Previous studies demonstrated that selenite induced cancer-cell apoptosis through multiple mechanisms; however, effects of selenite on microtubules in leukemic cells have not been demonstrated.

Methods: The toxic effect of selenite on leukemic HL60 cells was performed with cell counting kit 8. Selenite effects on cell cycle distribution and apoptosis induction were determined by flow cytometry.

Activation of p53 by sodium selenite switched human leukemia NB4 cells from autophagy to apoptosis.

It was revealed by our previous research that sodium selenite repressed autophagy accompanied by the induction of apoptosis in human leukemia NB4 cells. The inhibition of autophagy exerted a facilitative effect on apoptosis. In the present study, we further explored the mechanisms underlying the switch from autophagy to apoptosis and elucidated p53 played a key role.

[Effects of sodium selenite on the expressions of beta-catenin and its target cyclin D1 in colorectal cancer cells HCT 116 and SW480].

Objective: To explore the effects of sodium selenite on the expressions of beta-catenin and cyclin D1 in colorectal cancer cells HCT 116 and SW480.

Methods: HCT 116 and SW480 cells were treated by 10 micromol/L sodium selenite at different time points. The expressions and transcription of beta-catenin and cyclin D1 were detected by Western blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR), respectively.

Sodium selenite-induced activation of DAPK promotes autophagy in human leukemia HL60 cells.

Autophagy has been suggested as a possible mechanism for non-apoptotic death despite evidence from many species that autophagy represents a survival strategy of cells under stress. From our previous findings that supranutritional doses of sodium selenite induced apoptosis in human leukemia cells, now we show autophagic cell death occurred after selenite exposure in HL60, suggested an alternative mechanism for the potential therapeutic properties of selenite. Additionally, Death-associated Protein Kinase (DAPK) performed a significantly increased expression during this process, concomitantly with gradually decreased phosphorylation at Ser(308).

[The effects and mechanisms of erythropoietin on hepcidin of human monocytes].

Objective: To investigate the in vitro effect of erythropoietin (EPO) on hepcidin of monocytes and its molecular mechanisms.

Methods: Hepcidin and signaling molecules including C/EBPalpha, Smad1/5/8, p-Smad1/5/8 and p-STAT3 were detected by real time PCR and Western blot. THP-1 monocytes were stimulated by interleukin-6 (IL-6) or lipopolysaccharide (LPS).

Effects of cyclooxygenase-2 on human esophageal squamous cell carcinoma.

Aim: To study the relationship between the cyclooxygenase (COX)-2 gene and the proliferation and apoptosis of esophageal squamous carcinoma EC109 cells.

Methods: The techniques of RNA interference (RNAi) and cell transfection, as well as the levels of oncogenicity in nude mice, were used to study the role of COX-2 in the esophageal squamous carcinoma cell (ESCC) line EC109. Following RNAi and transfection, Western blotting analysis was used to determine the expression of the COX-2 protein.

Selenite induces apoptosis in colorectal cancer cells via AKT-mediated inhibition of β-catenin survival axis.

Mounting evidence reveals that selenium possesses chemotherapeutic potential against cancer cells. However, the molecular mechanisms underlying the anti-cancer effect of selenium remain elusive. In this study, with the aim to explore the detailed mechanisms how selenite induces apoptosis in colorectal cancer cells, we investigated the role of AKT/β-catenin signaling, a critical regulator of cell proliferation, survival and tumorigenesis, in selenite-induced apoptosis of colorectal cancer cells and xenograft tumors.

[Effect of erythropoietin on proinflammatory factors of human monocytes and its mechanisms].

Erythropoietin (EPO) is the major means of treating anemia of chronic disease (ACD) through stimulating hematopoiesis, inhibiting hepcidin and decreasing proinflammatory factors. Recently, it has been found that monocytes are another source of hepcidin. EPO can reduce the hepcidin stimulated by IL-6 in monocytes, it is assumed that EPO can reduce hepcidin indirectly by reducing IL-6.

Heat shock protein 90-mediated inactivation of nuclear factor-κB switches autophagy to apoptosis through becn1 transcriptional inhibition in selenite-induced NB4 cells.

Autophagy can protect cells while also contributing to cell damage, but the precise interplay between apoptosis and autophagy and the contribution of autophagy to cell death are still not clear. Previous studies have shown that supranutritional doses of sodium selenite promote apoptosis in human leukemia NB4 cells. Here, we report that selenite treatment triggers opposite patterns of autophagy in the NB4, HL60, and Jurkat leukemia cell lines during apoptosis and provide evidence that the suppressive effect of selenite on autophagy in NB4 cells is due to the decreased expression of the chaperone protein Hsp90 (heat shock protein 90), suggesting a novel regulatory function of Hsp90 in apoptosis and autophagy.