Therapeutic effect of Echinococcus granulosus cyst fluid on bacterial sepsis in mice.

BACKGROUND: The primary pathophysiological process of sepsis is to stimulate a massive release of inflammatory mediators to trigger systemic inflammatory response syndrome (SIRS), the major cause of multi-organ dysfunction and death. Like other helminths, Echinococcus granulosus induces host immunomodulation. We sought to determine whether E. granulosus cyst fluid (EgCF) displays a therapeutic effect on sepsis-induced inflammation and tissue damage in a mouse model. METHODS: The anti-inflammatory effects of EgCF were determined by in vitro culture with bone marrow-derived macrophages (BMDMs) and in vivo treatment of BALB/C mice with cecal ligation and puncture (CLP)-induced sepsis. The macrophage phenotypes were determined by flow cytometry, and the levels of cytokines in cell supernatants or in sera of mice were measured (ELISA). The therapeutic effect of EgCF on sepsis was evaluated by observing the survival rates of mice for 72 h after CLP, and the pathological injury to the liver, kidney, and lung was measured under a microscope. The expression of TLR-2/MyD88 in tissues was measured by western blot to determine whether TLR-2/MyD88 is involved in the sepsis-induced inflammatory signaling pathway. RESULTS: In vitro culture with BMDMs showed that EgCF promoted macrophage polarization to M2 type and inhibited lipopolysaccharide (LPS)-induced M1 macrophages. EgCF treatment provided significant therapeutic effects on CLP-induced sepsis in mice, with increased survival rates and alleviation of tissue injury. The EgCF conferred therapeutic efficacy was associated with upregulated anti-inflammatory cytokines (IL-10 and TGF-ß) and reduced pro-inflammatory cytokines (TNF-α and INF-γ). Treatment with EgCF induced Arg-1-expressed M2, and inhibited iNOS-expressed M1 macrophages. The expression of TLR-2 and MyD88 in EgCF-treated mice was reduced. CONCLUSIONS: The results demonstrated that EgCF confers a therapeutic effect on sepsis by inhibiting the production of pro-inflammatory cytokines and inducing regulatory cytokines. The anti-inflammatory effect of EgCF is carried out possibly through inducing macrophage polarization from pro-inflammatory M1 to regulatory M2 phenotype to reduce excessive inflammation of sepsis and subsequent multi-organ damage. The role of EgCF in regulating macrophage polarization may be achieved by inhibiting the TLR2/MyD88 signaling pathway.

circ0005027 Acting as a ceRNA Affects the Malignant Biological Behavior of Hypopharyngeal Squamous Cell Carcinoma by Modulating miR-548c-3p/CDH1 Axis.

Hypopharyngeal squamous cell carcinoma (HSCC) is a malignant tumor of head and neck. It was verified that circ0005027 was downregulated in HSCC tissues. Here, we aimed to investigate the function and specific regulatory mechanism of circ0005027 in HSCC. Ten pairs tissues of HSCC and adjacent para-cancer were collected. Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) measured circ0005027, miR-548c-3p, and Cadherin 1 (CDH1) mRNA expression. CCK-8 analyzed cell proliferation viability. Flow cytometry assay detected cell cycle and apoptosis rate. Clonal formation assay measured the clonal ability. Transwell detected cell invasion ability. Western blot was performed to detect CDH1, LAST1, p-LAST1, MST1, p-MST1, YAP1, p-YAP1, TAZ and p-TAZ protein level. Dual-luciferase, RIP and RNA pull-down assay identified the target relationship among circ0005027, miR-548c-3p and CDH1. circ0005027 was decreased in tissues and FaDu cells of HSCC. Overexpression of circ0005027 inhibited cell viability, G1-S transition, clonal formation, and invasion and increased cell apoptosis. circ0005027 acted as a ceRNA and decreased circ0005027 enhanced the malignant process of FaDu cells through sponging miR-548c-3p and inhibiting CDH1 expression. Overexpression of CDH1 activated YAP1/TAZ pathway and inhibited the growth of HSCC in vitro. circ0005027 might act as a potential biomarker for the progression and prognosis prediction in HSCC by regulating miR-548c-3p/CDH1/ YAP1/TAZ signaling pathway.

Understanding sorafenib-induced ferroptosis and resistance mechanisms: Implications for cancer therapy.

Sorafenib is an important first-line treatment option for liver cancer due to its well-characterized safety profile. While novel first-line drugs may have better efficacy than Sorafenib, they also have limitations such as worse safety and cost-effectiveness. In addition to inducing apoptosis, Sorafenib can also trigger ferroptosis, which has recently been recognized as an immunogenic cell death, unleashing new possibilities for cancer treatment. However, resistance to Sorafenib-induced ferroptosis remains a major challenge. To overcome this resistance and augment the efficacy of Sorafenib, a wide range of nanomedicines has been developed to amplify its pro-ferroptotic effects. This review highlights the mechanisms underlying Sorafenib-triggered ferroptosis and its resistance, and outlines innovative strategies, particularly nanomedicines, to overcome ferroptosis resistance. Moreover, we summarize molecular biomarkers that signify resistance to Sorafenib-mediated ferroptosis, which can assist in predicting therapeutic outcomes.

Analysis of Clinical Treatment of Laryngeal Stenosis After Radiotherapy and Supracricoid Partial Laryngectomy with Cricohyoidoepiglottopexy of Mid-stage and Advanced Laryngeal Cancer.

OBJECTIVE: To investigate the possible causes and treatment methods of laryngeal stenosis after radiotherapy following supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCPL-CHEP). METHODS: The data of seven patients with laryngeal stenosis after radiotherapy following SCPL-CHEP were analysed retrospectively. All patients were diagnosed with mid-stage or advanced laryngeal carcinoma before surgery, and the pathological type was squamous cell carcinoma. All patients met the requirements for SCPL-CHEP surgery. When laryngeal stenosis was found during the post-surgical follow-up period, patients were immediately given the appropriate treatment according to their conditions. RESULTS: All seven patients had laryngeal stenosis. One patient underwent granulation resection using a laryngoscope, four patients underwent granulation removal + low-temperature plasma ablation using a laryngoscope, and two patients underwent laryngeal dehiscence surgery + laryngotracheal T-tube placement. All patients recovered well after surgery, with patent airways. CONCLUSION: Laryngeal stenosis in patients with mid- and late-stage laryngeal carcinoma is one of the rare complications of SCPL-CHEP. Second-stage laryngeal dilatation can be selected according to the patient's laryngeal stenosis. Most patients with laryngeal stenosis can be extubated completely.

Knowledge, Attitudes, and Practices Toward COVID-19 Among Rural Residents of Hebei Province: A Cross-Sectional Survey.

OBJECTIVE: Coronavirus disease (COVID-19) has spread worldwide due to high infectivity. The social sexual environment in rural areas of China and the weak basic medical facilities may affect the treatment and transmission of the disease. The aim of this study was to understand the knowledge, attitudes, and practices (KAP) related to COVID-19 among residents in rural areas experiencing the epidemic and the factors, to provide a basis for further epidemic prevention and control. METHODS: The COVID-19 KAP of rural residents in Hebei Province was collected by the snowball sampling method. The COVID-19 KAP questionnaire was distributed on social platforms such as WeChat and QQ through a network questionnaire. RESULTS: The overall level of COVID-19 KAP in rural residents was good, but in terms of knowledge, the correct rate of isolation was 73.2%, the correct rates of 2 disinfection items were 72.3% and 77.4%, and the correct rate of hand-washing was 70.7%; 54.5% residents felt panic; 81.0% disinfected household items; and 84.9% washed their hands correctly. Residents still needed to strengthen these aspects. A binary logistic analysis showed that age, education, and participation in training were factors affecting the level of COVID-19 KAP. CONCLUSIONS: This study found that rural residents had good levels of COVID-19 KAP, but there were gaps in specific issues that warrant attention. We advocate training on COVID-19 for rural residents.

Role Mismatch in Medical Decision-Making Participation Is Associated with Anxiety and Depression in Family Members of Patients in the Intensive Care Unit.

This study aimed to investigate the mismatch between the preferred and actual roles in the medical decision-making of intensive care unit (ICU) patients' family members and the relationship between the role mismatch of family members' decisions and anxiety and depression syndromes. A total of 223 family members of ICU patients in the Affiliated Hospital of Jiangnan University in China were enrolled. The simple Chinese version of the Control Preference Scale was used to complete the surveys to assess the preferred and actual roles, and anxiety and depression syndromes were measured using the Generalized Anxiety Disorder-7 scale and Patient Health Questionnaire-9, respectively. For the preferred and actual roles, the active role rates were 16.1% and 8.1%, the cooperative role rates were 49.3% and 31.4%, and the passive role rates were 34.5% and 60.5%, respectively. The incidence of mismatch was 43.0% between the preferred and actual roles, and the consistency between their preferred and actual decision-making roles was poor (kappa = 0.309, P < 0.001). Family members with mismatched decision-making roles had significantly higher incidence rates of anxiety (90.6% vs. 57.5%, P < 0.001) and depression (86.5% vs. 63.0%, P < 0.001). Logistic regression analysis revealed that mismatches in decision-making roles remained independently associated with these outcomes after adjustment for family members' sociodemographic features. The results of the present study demonstrate that the preferred role of ICU patients' family members is mainly cooperative, and the actual role is mainly passive. The mismatch between the preferred and actual roles is associated with anxiety and depression among the ICU patients' family members.

Rigosertib inhibits MEK1-ERK pathway and alleviates lipopolysaccharide-induced sepsis.

BACKGROUND: Here, by using the lipopolysaccharide (LPS)-induced mice sepsis model, we treated septic wild-type (WT) mice or MEK1DD mice with rigosertib to evaluate its prospective effects on sepsis. METHODS: We also generated macrophages derived from bone marrow from WT or MEK1DD mice. These macrophages were pretreated with rigosertib and then induced with LPS or poly I:C. RESULTS: Rigosertib suppressed LPS or poly I:C-induced expression of inflammatory cytokines (tumor necrosis factor-alpha [TNF-α] and interleukin-6 [IL-6], and IL-23) in WT bone marrow-derived macrophages while failed to affect the upregulation of TNF-α and IL-6 in LPS-treated bone marrow-derived macrophages from MEK1DD mice. Rigosertib promoted survival rate, ameliorated lung injury, and reduced inflammatory cytokine levels in serum of WT septic mice. CONCLUSION: In contrast, the effects of rigosertib on sepsis were abrogated in septic MEK1DD mice, which had inducible constitutive activation of MEK1 signaling. Rigosertib alleviated LPS-induced sepsis inhibits MEK1/ERK signaling pathway.

CircRNA ZNF609 promotes angiogenesis in nasopharyngeal carcinoma by regulating miR-145/STMN1 axis.

Nasopharyngeal carcinoma (NPC) is the most common type of human malignant tumor in the head and neck, and tumor angiogenesis is essential for its development. Here, we showed that the circRNA ZNF609/microRNA (miR)-145/Stathmin 1 (STMN1) axis regulated angiogenesis in NPC.Circ-ZNF609, miR-145, and STMN1 expression in NPC cells and NPC samples were examined using qRT-PCR. The protein levels of STMN1, VEGFR1, and VEGFR2 were evaluated using western blotting. VEGF level was determined by ELISA. The proliferation of NPC cells and HUVECs was examined using a CCK-8 assay. Transwell assays and wound-healing assays were applied to assess the migration of NPC cells and HUVECs, respectively. Angiogenesis of HUVECs was evaluated by an angiogenesis assay. In addition, a dual-luciferase reporter assay and RNA pull-down assays were employed to verify the binding relationship between circ-ZNF609 and miR-145 as well as between miR-145 and STMN1. Here, we showed that circ-ZNF609 and STMN1 expression was increased, while miR-145 expression was decreased in NPC cells and NPC samples. Circ-ZNF609 may negatively regulate miR-145 expression by acting as a ceRNA. Silencing circ-ZNF609 suppressed cell proliferation, migration, and angiogenesis in NPC, while knockdown of miR-145 reversed these effects. In addition, we found that STMN1 was the downstream target of miR-145. MiR-145 overexpression suppressed cell proliferation, migration, and angiogenesis in NPC, which was abolished by STMN1 overexpression. Our data suggested that circ-ZNF609 promotes cell proliferation, migration, and angiogenesis in NPC by upregulating the expression of STMN1 by sponging miR-145 in NPC.

Effect of Humidity-Controlled Dehydration on Microbial Growth and Quality Characteristics of Fresh Wet Noodles.

Humidity-controlled dehydration (HCD) was innovatively applied in this paper to control the growth of microorganisms in fresh wet noodles (FWN). Effects of HCD treatment with different temperatures (40, 60 or 80 °C), relative humidity (RH, 50%, 70% or 90%) and treatment time (5-32 min) on the total plate count (TPC), the shelf-life, and qualities of FWN were investigated. The results showed that HCD reduced the initial microbial load on the fresh noodles and extended the shelf-life up to 14-15 days under refrigeration temperature (10 °C). A 1.39 log10 CFU/g reduction for the initial TPC was achieved after HCD treatment at the temperature of 60 °C and RH of 90%. HCD with higher RH had a more positive influence on quality improvement. The L* values, the apparent stickiness, and the cooking properties of the noodle body were improved by HCD while good sensory and texture quality of noodles were still maintained after the dehydration process.

Postoperative secondary aggravation of obstructive sleep apnea-hypopnea syndrome and hypoxemia with bilateral carotid body tumor: A case report.

BACKGROUND: Carotid body tumor (CBT) is a chemoreceptor tumor located in the carotid body, accounting for approximately 0.22% of head and neck tumors. Surgery is the main treatment method for the disease. CASE SUMMARY: We reviewed the diagnosis and treatment of one patient who had postoperative secondary aggravation of obstructive sleep apnea-hypopnea syndrome (OSAHS) and hypoxia after surgical resection of bilateral CBTs. This patient was admitted, and relevant laboratory and imaging examinations, and polysomnography (PSG) were performed. After the definitive diagnosis, continuous positive airway pressure (CPAP) treatment was given, which achieved good efficacy. CONCLUSION: This case suggested that aggravation of OSAHS and hypoxemia is possibly caused by the postoperative complications after bilateral CBTs, and diagnosis by PSG and CPAP treatment are helpful for this patient.

Berberine functions as a negative regulator in lipopolysaccharide -induced sepsis by suppressing NF-κB and IL-6 mediated STAT3 activation.

Sepsis is a deadly complication raised by bacterial pathogens-induced dysregulated innate inflammatory response. Thus, anti-inflammatory is a potential therapeutic treatment for septic patients. Numerous evidence exhibited that berberine possesses potent anti-inflammatory, anti-apoptotic and anti-oxidative activities. However, the effect of berberine on sepsis is not fully understood. The anti-inflammatory effect of berberine was evaluated using lipopolysaccharide (LPS)-induced macrophages differentiation model in vitro and using LPS/D-galactosamine-challenged septic mice model in vivo. The secreted protein levels were determined by ELISA assay. The multiple targets mRNA and protein levels were measured by quantitative RT-PCR and western blot assay, respectively. Our study demonstrated that administration of berberine significantly attenuated lung tissue injury, and potently increased the survival rate of septic mice by modulating excessive inflammatory response with negligible side-effects. We further found that berberine inhibited the expression of tumor necrosis factor (TNF)-α, interleukin-(IL)-1ß and IL-6 via suppressing nuclear factor kappa B subunit 1 (NF-κB) signaling activation. Our study strongly supported the concept that berberine may serve as a single drug or a promising adjuvant that can be used in conjunction with other medications for the treatment of septic patients.

Lactobacillus rhamnosus GG strain mitigated the development of obstructive sleep apnea-induced hypertension in a high salt diet via regulating TMAO level and CD4+ T cell induced-type I inflammation.

Obstructive sleep apnea (OSA) and high salt content in modern diet has been particularly implicated in systemic hypertension, leading to increased morbidity and mortality. Gut dysbiosis, associated with increased risk of systemic immunological imbalance, plays a causal role in the development of cardiovascular diseases. Here, we investigated the effect of Lactobacillus rhamnosus GG strain (LGG) on the development of hypertension induced by OSA and high salt diet. In this study, hypertension was modeled in rats by feeding a high salt diet (HSD) for 6 wk and exposuring to chronic intermittent hypoxia (CIH) during the sleep cycle. We found that OSA combined with HSD increased the severity of hypertension through increasing level of blood Trimethylamine-Oxide (TMAO), release of Th1-related cytokine (IFN-γ) and inhibition of anti-inflammatory cytokine (TGF-ß1), and affected the gut microbiome in rats, particularly by depleting Lactobacillus. In addition, expression of PERK1/2, PAkt and PmTOR increased in the aorta from rats with a CIH exposure and HSD. Consequently, treatment of model rats with LGG prevented aggravation of hypertension by reducing blood TMAO levels, modulating Th1/Th2 cytokine imbalance and suppressing phosphorylation levels of ERK1/2, Akt and mTOR. In line with these findings, our results connect high salt diet to the gut-immune axis and highlight the gut microbiome as a potential therapeutic target to counteract the development of OSA-induced hypertension basing on a high salt diet.

Dihydroartemisinin inhibits cell proliferation by induced G1 arrest and apoptosis in human nasopharyngealcarcinoma cells.

CONTEXT: Dihydroartemisinin (DHA) exhibits anticancer activity in a number of human cancer cells. However, it is still unknown whether DHA has anticancer effect on nasopharyngeal cancer (NPC) cells. AIMS: To investigate the anticancer activity of DHA on CNE-2 cells. MATERIALS AND METHODS: Cell cycleand invasion assay were used to detect the effect of DHA on CNE-2 cells. Protein molecular differences were examined by Western blot. RESULTS: DHA strongly inhibited cell proliferation by induced cell cycle G1 arrest and apoptosis in CNE-2 cells. In addition, cell motility, invasion, and colony formation were suppressed by DHA. CONCLUSIONS: DHA shows significant anticancer effects on human NPC cells, and may be a preventive and therapeutic agent against NPC.

[Apoptosis of nasopharyngeal carcinoma cells line CNE-2 induced by dihydroartemisinin and its possible mechanism].

OBJECTIVE: Dihydroartemisinin is a traditional anti-malarial drug, a derivative of the artemisinin, it has anti-tumor activity of a variety of tumor cells. This study investigated the effect of growth inhibition of nasopharyngeal carcinoma cells line CNE-2 induced by dihydroartemisinin and its possible mechanism. METHOD: The effect of DHA on the cell proliferation of CNE-2 was detected by CCK-8 assay with different concentrations and time. The effects of DHA on the cell apoptosis of CNE-2 were detected by Annexin V-FITC assay through flow cytometry and caspase-3 activity assay. RESULT: CCK-8 experimental results show that CNE-2 cell proliferation was suppressed with DHA treatment, as compared with the control group. DHA could induce marked apoptosis in CNE-2 by apoptosis assay, as compared with the control group, The percentages of apoptotic cells increased along with the increase of DHA concentrations in CNE-2; The activity of caspase-3 was increased following DHA treatment in a dose-dependent manner. CONCLUSION: DHA could effectively inhibit proliferation and induce apoptosis of human nasopharyngeal carcinoma cells line CNE-2, the possible mechanism DHA induce apoptosis of CNE-2 cells by upregulating the expression of caspase-3.