[Curcumin alleviates nuclear factor-κB/NOD-like receptor protein 3 mediated renal injury caused by acute respiratory distress syndrome through reducing mitochondrial oxidative stress].

OBJECTIVE: To evaluate the effect of curcumin on renal mitochondrial oxidative stress, nuclear factor-κB/NOD-like receptor protein 3 (NF-κB/NLRP3) inflammatory body signaling pathway and tissue cell injury in rats with acute respiratory distress syndrome (ARDS). METHODS: A total of 24 specific pathogen free (SPF)-grade healthy male Sprague-Dawley (SD) rats were randomly divided into control group, ARDS model group, and low-dose and high-dose curcumin groups, with 6 rats in each group. The ARDS rat model was reproduced by intratracheal administration of lipopolysaccharide (LPS) at 4 mg/kg via aerosol inhalation. The control group was given 2 mL/kg of normal saline. The low-dose and high-dose curcumin groups were administered 100 mg/kg or 200 mg/kg curcumin by gavage 24 hours after model reproduction, once a day. The control group and ARDS model group were given an equivalent amount of normal saline. After 7 days, blood samples were collected from the inferior vena cava, and the levels of neutrophil gelatinase-associated lipocalin (NGAL) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The rats were sacrificed, and kidney tissues were collected. Reactive oxygen species (ROS) levels were determined by ELISA, superoxide dismutase (SOD) activity was detected using the xanthine oxidase method, and malondialdehyde (MDA) levels were determined by colorimetric method. The protein expressions of hypoxia-inducible factor-1α (HIF-1α), caspase-3, NF-κB p65, and Toll-like receptor 4 (TLR4) were detected by Western blotting. The mRNA expressions of HIF-1α, NLRP3, and interleukin-1ß (IL-1ß) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Renal cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). The morphological changes in renal tubular epithelial cells and mitochondria were observed under a transmission electron microscope. RESULTS: Compared with the control group, the ARDS model group exhibited kidney oxidative stress and inflammatory response, significantly elevated serum levels of kidney injury biomarker NGAL, activated NF-κB/NLRP3 inflammasome signaling pathway, increased kidney tissue cell apoptosis rate, and renal tubular epithelial cell damage and mitochondrial integrity destruction under transmission electron microscopy, indicating successful induction of kidney injury. Following curcumin intervention, the injury to renal tubular epithelial cells and mitochondria in the rats was significantly mitigated, along with a noticeable reduction in oxidative stress, inhibition of the NF-κB/NLRP3 inflammasome signaling pathway, and a significant decrease in kidney tissue cell apoptosis rate, demonstrating a certain dose-dependency. Compared with the ARDS model group, the high-dose curcumin group exhibited significantly reduced serum NGAL levels and kidney tissue MDA and ROS levels [NGAL (µg/L): 13.8±1.7 vs. 29.6±2.7, MDA (nmol/g): 115±18 vs. 300±47, ROS (kU/L): 75±19 vs. 260±15, all P < 0.05], significantly down-regulated protein expressions of HIF-1α, caspase-3, NF-κB p65, and TLR4 in the kidney tissue [HIF-1α protein (HIF-1α/ß-actin): 0.515±0.064 vs. 0.888±0.055, caspase-3 protein (caspase-3/ß-actin): 0.549±0.105 vs. 0.958±0.054, NF-κB p65 protein (NF-κB p65/ß-actin): 0.428±0.166 vs. 0.900±0.059, TLR4 protein (TLR4/ß-actin): 0.683±0.048 vs. 1.093±0.097, all P < 0.05], and significantly down-regulated mRNA expressions of HIF-1α, NLRP3, and IL-1ß [HIF-1α mRNA (2-ΔΔCt): 2.90±0.39 vs. 9.49±1.87, NLRP3 mRNA (2-ΔΔCt): 2.07±0.21 vs. 6.13±1.32, IL-1ß mRNA (2-ΔΔCt): 1.43±0.24 vs. 3.95±0.51, all P < 0.05], and significantly decreased kidney tissue cell apoptosis rate [(4.36±0.92)% vs. (27.75±8.31)%, P < 0.05], and significantly increased SOD activity (kU/g: 648±34 vs. 430±47, P < 0.05). CONCLUSIONS: Curcumin can alleviate kidney injury in ARDS rats, and its mechanism may be related to the increasing in SOD activity, reduction of oxidative stress, and inhibition of the activation of the NF-κB/NLRP3 inflammasome signaling pathway.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Infectious diseases prevention and control using an integrated health big data system in China.

BACKGROUND: The Yinzhou Center for Disease Prevention and Control (CDC) in China implemented an integrated health big data platform (IHBDP) that pooled health data from healthcare providers to combat the spread of infectious diseases, such as dengue fever and pulmonary tuberculosis (TB), and to identify gaps in vaccination uptake among migrant children. METHODS: IHBDP is composed of medical data from clinics, electronic health records, residents' annual medical checkup and immunization records, as well as administrative data, such as student registries. We programmed IHBDP to automatically scan for and detect dengue and TB carriers, as well as identify migrant children with incomplete immunization according to a comprehensive set of screening criteria developed by public health and medical experts. We compared the effectiveness of the big data screening with existing traditional screening methods. RESULTS: IHBDP successfully identified six cases of dengue out of a pool of 3972 suspected cases, whereas the traditional method only identified four cases (which were also detected by IHBDP). For TB, IHBDP identified 288 suspected cases from a total of 43,521 university students, in which three cases were eventually confirmed to be TB carriers through subsequent follow up CT or T-SPOT.TB tests. As for immunization screenings, IHBDP identified 240 migrant children with incomplete immunization, but the traditional door-to-door screening method only identified 20 ones. CONCLUSIONS: Our study has demonstrated the effectiveness of using IHBDP to detect both acute and chronic infectious disease patients and identify children with incomplete immunization as compared to traditional screening methods.

[Acupoint selection rules of acupuncture for pseudobulbar palsy dysphagia].

OBJECTIVE: To analyze the acupoint selection rules of acupuncture for pseudobulbar palsy dysphagia using data mining technology. METHODS: The literature of acupuncture for pseudobulbar palsy dysphagia published from January 1, 1990 to May 1, 2021 was retrieved from CNKI, SinoMed, Wanfang, VIP, and PubMed databases. Acupuncture prescription database was established. The frequency of acupoint selection was analyzed by Microsoft Excel 2016; Apriori algorithm was used to analyze the association rules and draw the high-frequency acupoint co-occurrence network diagram; SPSS21.0 was used to perform clustering analysis. RESULTS: A total of 87 literature was included, involving 89 acupuncture prescriptions and 71 acupoints. Fengchi (GB 20) was the most frequently-used acupoint; the commonly-selected meridians were gallbladder meridian, conception vessel, governor vessel and stomach meridian; the acupoints located at the neck were the most frequently-used acupoints; the crossing points were commonly selected among the special acupoints. The most commonly-used acupoint combination was Jinjin (EX-HN 12) plus Yuye (EX-HN 13). CONCLUSION: The modern acupuncture for pseudobulbar palsy dysphagia usually selects local acupoints, especially the neck acupoints such as Fengchi (GB 20) and Lianquan (CV 23). The acupoints in the front and back are concurrently selected with needles towards the disease location.

The Association Between Sleep Disorders and Incidence of Dry Eye Disease in Ningbo: Data From an Integrated Health Care Network.

PURPOSE: To investigate the association between sleep disorders and dry eye disease (DED) in Ningbo, China. METHODS: Our data came from the Yinzhou Health Information System (HIS), including 257932 patients and was based on a 1:1 matching method (sleep disorder patients vs. patients without sleep disorders) during 2013-2020. Sleep disorders and DED were identified using ICD-10 codes. Cox proportional hazards regression was used to identify the association between sleep disorders and DED. RESULTS: The eight-year incidence of DED was significantly higher in participants with diagnosis of sleep disorders (sleep disorders: 50.66%, no sleep disorders: 16.48%, P < 0.01). Sleep disorders were positively associated with the diagnosis of DED (HR: 3.06, 95% CI: 2.99-3.13, P < 0.01), when sex, age, hypertension, diabetes and other systemic diseases were adjusted. In the sleep disorders patients, advancing age, female sex, and presence of coexisting disease (hypertension, diabetes, hyperlipidemia, thyroid disease, depression, heart disease, and arthritis) were significantly associated with the development of DED by the multivariate cox regression analysis (all P < 0.05).In addition, there was a significantly positive association between estazolam and the incidence of DED in both sleep disorder and non-sleep disorder groups (all P < 0.05). CONCLUSIONS: Sleep disrder was associated with a three-time increased risk of DED. This association can be helpful in effective management of both sleep disorders and DED.

Formononetin Protects LPS-Induced Mastitis Through Suppressing Inflammation and Enhancing Blood-Milk Barrier Integrity via AhR-Induced Src Inactivation.

Formononetin (FOR), a natural flavonoid derived from Radix Astragali, has been reported to have anti-inflammatory and anti-oxidative effects. However, its protective mechanism against mastitis is still unknown. Nuclear factor kappa-B (NF-κB) signaling pathway plays an important role in inflammation, especially mastitis. Aryl hydrocarbon receptor (AhR) is involved in inflammatory regulation and defense against diseases. We investigated the protective effect of FOR on LPS-induced mastitis in mice and the effect of Ahr and NF-κB signaling pathways on the development of mastitis. In this study, mastitis model was induced by LPS injection through the nipple duct. Protective effect of FOR on LPS-induced mastitis was assessed by FOR pretreatment. The protective mechanism of FOR against mastitis was further investigated using LPS stimulation on mouse mammary epithelial cells EpH4-Ev. The results showed that LPS-induced mammary histological injury was inhibited by FOR. FOR significantly inhibited LPS-induced MPO activity. FOR administration enhanced the integrity of blood-milk barrier. In vitro and in vivo experiments showed that FOR inhibited LPS-induced NF-κB signaling pathway activation and the production of inflammatory factors TNF-α and IL-1ß. Moreover, FOR increased the expression of tight junction protein and enhanced blood-milk barrier integrity. LPS activated AhR and Src expression. But FOR induced significant increase in AhR inhibited Src phosphorylation to exert anti-inflammatory effects. In addition, AhR antagonist CH223191 reversed the inhibition of FOR on Src expression. And the inhibition of FOR on NF-κB activation and inflammatory cytokine production were reversed by AhR antagonist CH223191. In conclusion, FOR had protective effects against LPS-induced mastitis via suppressing inflammation and enhancing blood-milk barrier integrity via AhR-induced Src inactivation.

Anti-IL-17A antibody-associated de novo vitiligo: Case report and review of literature.

Interleukin (IL)-17 inhibitor is a biological therapy approved for moderate to severe psoriasis and psoriatic arthritis. The common adverse events of IL-17 inhibitor include injection site reaction, infections, nasopharyngitis, and headache. However, vitiligo associated with the use of IL-17 inhibitors was rarely reported in the previous literature. Here we described a woman who developed de novo vitiligo after 4 months of IL-17A inhibitor treatment for psoriasis and psoriatic arthritis. Upon discontinuation of IL-17A inhibitor and shifting to a broader T cell inhibitor-cyclosporine, our patient had control of both psoriasis and vitiligo and achieved 75% repigmentation after 3 months of oral cyclosporine without phototherapy. Due to the increasing use of anti-IL-17 biologics in psoriasis patients, clinicians should inquire about vitiligo's history before treatment and inform patients of the possible adverse effects.

[Retracted] In vitro antitumor activity of the ethyl acetate extract Potentilla chinensis in osteosarcoma cancer cells.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that several figures bore striking similarities to other papers that were published at around the same time written by different authors based in different research institutions. Fig. 3 (in colour) was essentially the same as a greyscale figure (Fig. 4) in a paper published in Oncology Reports, which has now been retracted [Wan G, Tao J­G, Wang G­D, Liu S­P, Zhao H­X and Liang Q­D: 3­ß­Εrythrodiol isolated from Conyza canadensis inhibits MKN­45 human gastric cancer cell proliferation by inducing apoptosis, cell cycle arrest, DNA fragmentation, ROS generation and reduces tumor weight and volume in mouse xenograft mode. Oncol Rep 35: 2328­2338, 2016]. Furthermore, Figs. 5 and 6 in the above paper appeared to share data with Figs. 7 and 11, respectively, in a paper published in Phytomedicine [Sui C­G, Meng F­D and Jiang Y­h: Antiproliferative activity of rosamultic acid is associated with induction of apoptosis, cell cycle arrest, inhibition of cell migration and caspase activation in human gastric cancer (SGC­7901) cells. Phyomedicine 22: 796­806, 2015]. After having conducted an independent investigation in the Editorial Office, the Editor of Molecular Medicine Reports has determined that the above paper should be retracted from the Journal on account of a lack of confidence concerning the originality and the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [the original article was published in Molecular Medicine Reports 14: 3634­3640, 2016; DOI: 10.3892/mmr.2016.5679].

Effect of the transcription factor YY1 on the development of pancreatic endocrine and exocrine tumors: a narrative review.

Pancreatic tumors are classified into endocrine and exocrine types, and the clinical manifestations in patients are nonspecific. Most patients, especially those with pancreatic ductal adenocarcinoma (PDAC), have lost the opportunity to receive for the best treatment at the time of diagnosis. Although chemotherapy and radiotherapy have shown good therapeutic results in other tumors, their therapeutic effects on pancreatic tumors are minimal. A multifunctional transcription factor, Yin-Yang 1 (YY1) regulates the transcription of a variety of important genes and plays a significant role in diverse tumors. Studies have shown that targeting YY1 can improve the survival time of patients with tumors. In this review, we focused on the mechanism by which YY1 affects the occurrence and development of pancreatic tumors. We found that a YY1 mutation is specific for insulinomas and has a role in driving the degree of malignancy. In addition, changes in the circadian network are a key causative factor of PDAC. YY1 promotes pancreatic clock progression and induces malignant changes, but YY1 seems to act as a tumor suppressor in PDAC and affects many biological behaviors, such as proliferation, migration, apoptosis and metastasis. Our review summarizes the progress in understanding the role of YY1 in pancreatic endocrine and exocrine tumors and provides a reasonable assessment of the potential for therapeutic targeting of YY1 in pancreatic tumors.

Liuzijue is a promising exercise option for rehabilitating discharged COVID-19 patients.

BACKGROUND: Among discharged COVID-19 patients, the health-related quality of life is poor, and patients suffer from significant physical and psychological impairment. This study was designed to investigate the effects of Liuzijue exercise on the rehabilitation of COVID-19 patients. METHODS: Thirty three eligible patients with COVID-19 were enrolled in the study after discharge. All the participants practiced Liuzijue exercise once per day for 20 minutes over 4 weeks. Data were collected at baseline and the end of the intervention. Primary outcomes involved functional capacity and secondary outcomes involved quality of life. RESULTS: The maximal inspiratory pressure (MIP), peak inspiratory flow (PIF), and diaphragm movement in deep breathing (DM-DB) of patients increased significantly after 4 weeks of intervention. The dyspnea was also alleviated and exercise capacity was significantly improved. In terms of quality of life, physical functioning and role-physical scores were significantly increased. Moreover, Liuzijue could significantly alleviate the depression and anxiety status of the patients. CONCLUSION: Liuzijue exercise is a viable alternative home exercise program that produced better functional capacity and quality of life in discharged patients with COVID-19. These findings also showed the necessity of rehabilitation intervention for cured COVID-19 patients.

Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management.

Rheumatoid arthritis (RA) is a chronic inflammatory syndrome designated by synovial joint inflammation leading to cartilage degradation and bone damage as well as progressive disability. Synovial inflammation is promoted through the infiltration of mononuclear immune cells, dominated by CD4+ T cells, macrophages and dendritic cells (DCs), together with fibroblast-like synoviocytes (FLS), into the synovial compartment. Berberine is a bioactive isoquinoline alkaloid compound showing various pharmacological properties that are mainly attributed to immunomodulatory and anti-inflammatory effects. Several lines of experimental study have recently investigated the therapeutic potential of berberine and its underlying mechanisms in treating RA condition. The present review aimed to clarify determinant cellular and molecular targets of berberine in RA and found that berberine through modulating several signalling pathways involved in the joint inflammation, including PI3K/Akt, Wnt1/ß-catenin, AMPK/lipogenesis and LPA/LPA1 /ERK/p38 MAPK can inhibit inflammatory proliferation of FLS cells, suppress DC activation and modulate Th17/Treg balance and thus prevent cartilage and bone destruction. Importantly, these molecular targets may explore new therapeutic targets for RA treatment.

Vitamin D supplementation and the outcomes of critically ill adult patients: a systematic review and meta-analysis of randomized controlled trials.

This meta-analysis assessed the association between vitamin D supplementation and the outcomes of critically ill adult patients. A literature search was conducted using the PubMed, Web of Science, EBSCO, Cochrane Library, Ovid MEDLINE, and Embase databases until March 21, 2020. We only included randomized controlled trials (RCTs) comparing the efficacy of vitamin D supplementation with placebo in critically ill adult patients. The primary outcome was their 28-day mortality. Overall, 9 RCTs with 1867 patients were included. In the pooled analysis of the 9 RCTs, no significant difference was observed in 28-day mortality between the vitamin D supplementation and placebo groups (20.4% vs 21.7%, OR, 0.73; 95% CI, 0.46-1.15; I2 = 51%). This result did not change as per the method of vitamin D supplementation (enteral route only: 19.9% vs 18.2%, OR, 1.19; 95% CI, 0.88-1.57; I2 = 10%; intramuscular or intravenous injection route: 25.6% vs 40.8%, OR, 0.48; 95% CI, 0.21-1.06; I2 = 19%) or daily dose (high dose: 20.9% vs 19.8%, OR, 0.83; 95% CI, 0.51-1.36; I2 = 53%; low dose: 15.6% vs 21.3%, OR, 0.74; 95% CI, 0.32-1.68; I2 = 0%). No significant difference was observed between the vitamin D supplementation and placebo groups regarding the length of ICU stay (standard mean difference [SMD], - 0.30; 95% CI, - 0.61 to 0.01; I2 = 60%), length of hospital stay (SMD, - 0.17; 95% CI, - 041 to 0.08; I2 = 65%), and duration of mechanical ventilation (SMD, - 0.41; 95% CI, - 081 to 0.00; I2 = 72%). In conclusion, this meta-analysis suggested that the administration of vitamin D did not provide additional advantages over placebo for critically ill patients. However, additional studies are needed to confirm our findings.

Sulphonylureas monotherapy and risk of hospitalization for heart failure in patients with type 2 diabetes mellitus: A population-based cohort study in China.

PURPOSE: The risk of heart failure associated with sulphonylureas is unclear. We evaluated the association between sulphonylureas and hospitalization of heart failure (HHF) in patients with type 2 diabetes mellitus (T2DM) in China. METHODS: A retrospective cohort study was implemented using the Yinzhou Regional Health Care Database (YRHCD). We identified 15 752 adult patients with T2DM who were newly exposed to sulphonylurea monotherapy (N = 12 487) or acarbose monotherapy (N = 3265) from January 2010 to September 2016. Cox proportional hazards models weighted by inverse probability of treatment weights were used to compare the risk of HHF between initiators of sulphonylurea and acarbose. RESULTS: During a median follow-up of 0.55 (0.49, 1.11) and 0.49 (0.35, 0.70) years for sulphonylureas and acarbose initiators separately, 320 patients developed HHF, with 279 events in sulphonylureas group, and 41 events in acarbose group. The incidence rates of HHF among sulphonylureas initiators and acarbose initiators were 22.2 (95% CI 19.6-24.9) and 18.3 (95% CI 13.2-24.9) per 1000 person-years, respectively. The adjusted hazard ratio (aHR) of HHF for sulphonylureas vs acarbose was 1.61 (95% CI 1.14-2.27). When stratified by history of heart failure, aHR was 1.55 (95% CI 0.79-3.06) in patients with a history of heart failure, and 1.64 (95% CI 1.10-2.45) in patients with no history of heart failure. CONCLUSIONS: Our study suggested that use of sulphonylureas monotherapy compared with acarbose monotherapy for initial treatment of T2DM for approximately 0.5 years are significantly associated with a higher risk of HHF.

Applications of Inorganic Nanomaterials in Photothermal Therapy Based on Combinational Cancer Treatment.

BACKGROUND: Cancer is one of the major causes of death and is difficult to cure using existing clinical therapies. Clinical cancer treatments [such as surgery, chemotherapy (CHT), radiotherapy (RT) and immunotherapy (IT)] are widely used but they have limited therapeutic effects and unavoidable side effects. Recently, the development of novel nanomaterials offers a platform for combinational therapy (meaning a combination of two or more therapeutic agents) which is a promising approach for cancer therapy. Recent studies have demonstrated several types of nanomaterials suitable for photothermal therapy (PTT) based on a near-infrared (NIR) light-responsive system. PTT possesses favorable properties such as being low in cost, and having high temporospatial control with minimal invasiveness. However, short NIR light penetration depth limits its functions. METHODS: In this review, due to their promise, we focus on inorganic nanomaterials [such as hollow mesoporous silica nanoparticles (HMSNs), tungsten sulfide quantum dots (WS2QDs), and gold nanorods (AuNRs)] combining PTT with CHT, RT or IT in one treatment, aiming to provide a comprehensive understanding of PTT-based combinational cancer therapy. RESULTS: This review found much evidence for the use of inorganic nanoparticles for PTT-based combinational cancer therapy. CONCLUSION: Under synergistic effects, inorganic nanomaterial-based combinational treatments exhibit enhanced therapeutic effects compared to PTT, CHT, RT, IT or PDT alone and should be further investigated in the cancer field.

Current understanding of metal ions in the pathogenesis of Alzheimer's disease.

Background: The homeostasis of metal ions, such as iron, copper, zinc and calcium, in the brain is crucial for maintaining normal physiological functions. Studies have shown that imbalance of these metal ions in the brain is closely related to the onset and progression of Alzheimer's disease (AD), the most common neurodegenerative disorder in the elderly. Main body: Erroneous deposition/distribution of the metal ions in different brain regions induces oxidative stress. The metal ions imbalance and oxidative stress together or independently promote amyloid-ß (Aß) overproduction by activating ß- or γ-secretases and inhibiting α-secretase, it also causes tau hyperphosphorylation by activating protein kinases, such as glycogen synthase kinase-3ß (GSK-3ß), cyclin-dependent protein kinase-5 (CDK5), mitogen-activated protein kinases (MAPKs), etc., and inhibiting protein phosphatase 2A (PP2A). The metal ions imbalances can also directly or indirectly disrupt organelles, causing endoplasmic reticulum (ER) stress; mitochondrial and autophagic dysfunctions, which can cause or aggravate Aß and tau aggregation/accumulation, and impair synaptic functions. Even worse, the metal ions imbalance-induced alterations can reversely exacerbate metal ions misdistribution and deposition. The vicious cycles between metal ions imbalances and Aß/tau abnormalities will eventually lead to a chronic neurodegeneration and cognitive deficits, such as seen in AD patients. Conclusion: The metal ions imbalance induces Aß and tau pathologies by directly or indirectly affecting multiple cellular/subcellular pathways, and the disrupted homeostasis can reversely aggravate the abnormalities of metal ions transportation/deposition. Therefore, adjusting metal balance by supplementing or chelating the metal ions may be potential in ameliorating AD pathologies, which provides new research directions for AD treatment.

The YY1/miR-548t-5p/CXCL11 signaling axis regulates cell proliferation and metastasis in human pancreatic cancer.

Pancreatic cancer (PC) is a malignant tumor with a poor prognosis and high mortality. However, the biological role of miR-548t-5p in PC has not been reported. In this study, we found that miR-548t-5p expression was significantly decreased in PC tissues compared with adjacent tissues, and that low miR-548t-5p expression was associated with malignant PC behavior. In addition, high miR-548t-5p expression inhibited the proliferation, migration, and invasion of PC cell lines. Regarding the molecular mechanism, the luciferase reporter gene, chromatin immunoprecipitation (ChIP), and functional recovery assays revealed that YY1 binds to the miR-548t-5p promoter and positively regulates the expression and function of miR-548t-5p. miR-548t-5p also directly regulates CXCL11 to inhibit its expression. A high level of CXCL11 was associated with worse Tumor Node Metastasis (TNM) staging in patients with PC, enhancing proliferation and metastasis in PC cells. Our study shows that the YY1/miR-548t-5p/CXCL11 axis plays an important role in PC and provides a new potential candidate for the treatment of PC.

Ping weisan alleviates chronic colitis in mice by regulating intestinal microbiota composition.

ETHNOPHARMACOLOGICAL RELEVANCE: Ping weisan (PWS), a complex formulation used in traditional Chinese medicine, is first described in 1107 AD and published in the Prescriptions of Taiping Benevolent Dispensary. We have previously confirmed that PWS has the effect of alleviating DSS-induced chronic ulcerative colitis (UC) in mice. AIM OF THE STUDY: We aimed to examine whether PWS protects mice from chronic UC by regulating intestinal microbiota composition. MATERIALS AND METHODS: Chronic colitis was induced in C57BL/6 mice with 2.5% DSS in drinking water. PWS (8 g/kg) was orally administered throughout the experiment. Body weight changes, stool consistency and myeloperoxidase (MPO) activity were measured in these mice. Interleukin-17A (IL-17A) and interferon gamma (IFN-γ) mRNA levels were detected by qRT-PCR. The alterations of fecal microflora were investigated by 16S rRNA sequencing. Furthermore, intestinal tight junction protein including occludin, and serum lipopolysaccharide (LPS) level were also detected. RESULTS: PWS relieved DSS-induced loss of body weight, and improved stool consistency and MPO activity in mice. The levels of IL-17A and IFN-γ mRNA were also reduced after treatment with PWS. PWS not only regulated occludin level but also decreased serum LPS. We further showed DSS-induced changes in intestinal microbial composition and richness are significantly regulated by PWS. PWS treatment significantly decreased the abundance of Bacteroidetes, but increased the abundance of Firmicutes in chronic UC mice induced by DSS. CONCLUSIONS: Combining with our previous results, we found that PWS could exert anti-UC role by rebalancing intestinal bacteria.

miR-335 Acts as a Tumor Suppressor and Enhances Ionizing Radiation-Induced Tumor Regression by Targeting ROCK1.

Recent development of integrative therapy against melanoma combines surgery, radiotherapy, targeted therapy, and immunotherapy; however, the clinical outcomes of advanced stage and recurrent melanoma are poor. As a skin cancer, melanoma is generally resistant to radiotherapy. Hence, there is an urgent need for evaluation of the mechanisms of radioresistance. The present study identified miR-335 as one of the differential expression of miRNAs in recurrent melanoma biopsies post-radiotherapy. The expression of miR-335 declined in melanoma tissues compared to the adjacent tissues. Moreover, miR-335 expression correlated with advanced stages of melanoma negatively. Consistent with the prediction of STARBASE and miRDB database, miR-335 targeted ROCK1 via binding with 3'-UTR of ROCK1 directly, resulting in attenuation of proliferation, migration, and radioresistance of melanoma cells. The authors validated that overexpression of miR-335 enhanced X-ray-induced tumor regression by B16 mouse models. Briefly, the present findings gained insights into miR-335/ROCK1-mediated radiosensitivity and provided a promising therapeutic strategy for improving radiotherapy against melanoma.

YY1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/MAPK and PI3K/AKT pathways.

BACKGROUND: Pancreatic cancer (PDAC) is a highly invasive cancer with poor prognosis. Recent research has found that the transcription factor Yin Yang 1 (YY1) plays an inhibitory role in the development of pancreatic cancer. It has been reported that tubulin polymerisation-promoting protein (TPPP) plays an indispensable role in a variety of tumours, but its expression and role in pancreatic cancer have not yet been elucidated. METHODS: In this study, we performed ChIP-sequencing and found that YY1 directly binds to the promoter region of TPPP. The expression of TPPP in pancreatic cancer was detected by western blotting and immunohistochemistry. Four-week-old male BALB/c-nude mice were used to assess the effect of TPPP on pancreatic cancer. RESULTS: Immunohistochemistry revealed that TPPP was expressed at low levels in pancreatic cancer tissues, and was associated with blood vessel invasion. The results from vivo experiments have showed that TPPP could enhance the migration and invasion of pancreatic cancer. Further experiments showed that YY1 could inhibit the migration, invasion and angiogenesis of pancreatic cancer cells by downregulating TPPP via p38/MAPK and PI3K/AKT pathways. CONCLUSION: Our study demonstrates that TPPP may act as a promoter and may serve as a novel target for the treatment of pancreatic cancer.

YY1 inhibits the migration and invasion of pancreatic ductal adenocarcinoma by downregulating the FER/STAT3/MMP2 signaling pathway.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and a high mortality rate. The transcription factor YY1 acts as an inhibitor of many types of tumors. We found that YY1 knockdown promoted the invasion and migration of PANC-1 and BxPC-3 cells; FER knockdown partially restored the promotion of pancreatic cancer caused by YY1 knockdown. In vivo experiments yielded the same results. According to luciferase reporter gene, electrophoretic mobility shift (EMSA) and chromatin immunoprecipitation (ChIP) assays, YY1 directly binds to the FER promoter region. Moreover, higher level FER expression results in a worse TNM stage and prognosis for patients with PDAC. Furthermore, by downregulating FER, YY1 inhibits the formation of the STAT3-MMP2 complex, thereby suppressing expression of MMP2 and ultimately inhibiting the migration and invasion of pancreatic cancer. Our study demonstrates that the YY1/FER/STAT3/MMP2 axis is associated with the progression of pancreatic cancer and may provide a new therapeutic target for the treatment of pancreatic cancer.