Rosa sterilis Juice Alleviated Breast Cancer by Triggering the Mitochondrial Apoptosis Pathway and Suppressing the Jak2/Stat3 Pathway.

Rosa sterilis (RS) is a characteristic fruit in southwestern China that has numerous health benefits; however, its pharmacological effect needs further clarification, especially with respect to the exploration of its potential anti-breast-cancer effect, as there are still knowledge gaps in this regard. This study was designed to investigate the protective effects of Rosa sterilis juice (RSJ) on breast cancer (BC) through in vitro cellular experiments and by establishing mouse 4T1 breast xenograft tumors. This study also had the aim of elucidating RSJ's underlying mechanisms. RSJ can inhibit cell proliferation, affect cell morphology, and impact the clone formation ability of BC; furthermore, it can promote apoptosis by triggering the mitochondrial apoptosis pathway. In mouse 4T1 breast xenograft tumors, RSJ markedly inhibited tumor growth, relieved the pathological lesions, lowered the expression of Ki67, and regulated the expression of the apoptosis-associated protein. Moreover, we observed that RSJ can inhibit the Jak2/Stat3 signaling pathway both in vivo and in vitro. Overall, our research reveals that RSJ can alleviate BC by triggering the mitochondrial apoptosis pathway and suppressing the Jak2/Stat3 pathway, providing new dietary intervention strategies for BC.

Ex-situ machine perfusion in clinical liver transplantation: Current practices and future directions.

Ex-situ machine perfusion of the liver has surmounted traditional limitations associated with static cold storage in the context of organ preservation. This innovative technology has changed the landscape of liver transplantation by mitigating ischemia perfusion injury, offering a platform for continuous assessment of organ quality, and providing an avenue for optimizing use of traditionally marginal allografts. This review summarizes the contemporary clinical applications of machine perfusion devices, and discusses potential future strategies for real-time viability assessment, therapeutic interventions, and modulation of organ function after recovery.

Differentiation between viral and autoimmune limbic encephalitis: a prospective cohort study with development and validation of a diagnostic model.

BACKGROUND: Distinguishing between viral encephalitis (VE) and autoimmune limbic encephalitis (ALE) presents a clinical challenge due to the overlap in symptoms. We aimed to develop and validate a diagnostic prediction model to differentiate VE and ALE. METHODS: A prospective observational multicentre cohort study, which continuously enrolled patients diagnosed with either ALE or VE from October 2011 to April 2023. The demographic data, clinical features, and laboratory test results were collected and subjected to logistic regression analyses. The model was displayed as a web-based nomogram and then modified into a scored prediction tool. Model performance was assessed in both derivation and external validation cohorts. RESULTS: A total of 2423 individuals were recruited, and 1001 (496 VE, 505 ALE) patients were included. Based on the derivation cohort (389 VE, 388 ALE), the model was developed with eight variables including age at onset, acuity, fever, headache, nausea/vomiting, psychiatric or memory complaints, status epilepticus, and CSF white blood cell count. The model showed good discrimination and calibration in both derivation (AUC 0.890; 0.868-0.913) and external validation (107 VE, 117 ALE, AUC 0.872; 0.827-0.917) cohorts. The scored prediction tool had a total point that ranged from - 4 to 10 also showing good discrimination and calibration in both derivation (AUC 0.885, 0.863-0.908) and external validation (AUC 0.868, 0.823-0.913) cohorts. CONCLUSIONS: The prediction model provides a reliable and user-friendly tool for differentiating between the VE and ALE, which would benefit early diagnosis and appropriate treatment and alleviate economic burdens on both patients and society.

Sarcopenia in cirrhotic patients: Does frailty matter while waiting for a liver transplant?

Sarcopenia reflects patient frailty and should be routinely assessed due to its high prevalence in cirrhotic patients awaiting liver transplants. Pre-transplant nutritional optimization should be tailored for patients with a definitive diagnosis of sarcopenia, therefore improving functional status at transplant and reducing post-transplant mortality. Hepatologists and transplant surgeons should have raised awareness regarding sarcopenia and the reflected frailty that hinder posttransplant outcomes. The policymakers should also take into account when modifying the organ allocation model that sarcopenia or frailty might become a decisive factor in allocating organs for cirrhotic patients, in order to ensure post-transplant survival and quality of life.

Liver Transplantation for Hepatocellular Carcinoma: A Narrative Review and A Glimpse into The Future.

Liver transplantation (LT) is a highly effective treatment for carefully selected patients with hepatocellular carcinoma (HCC). In this review, we explored the development of LT selection criteria and organ allocation policies, comparing original data to underscore their historical progression into the intricate task of quantitatively estimating pre- and post-LT survivals. We emphasized the role of biomarkers such as serum alpha-fetoprotein, Des-gamma-carboxy-prothrombin, circulating tumor cells, and circulating tumor DNA in predicting patient outcomes. Additionally, we examined the transplant-associated survival benefits and the difficulties in accurately calculating these benefits. We also reviewed recent advancements in targeted therapy and checkpoint inhibitors for advanced, inoperable HCC and projected their integration into LT for HCC. We further discussed the growing use of living donor liver transplants in the United States and compared its outcomes with those of deceased donor liver transplants. Furthermore, we examined the progress in machine perfusion techniques, which have shown potential in improving patient outcomes and enlarging the donor pool. These advancements present opportunities to enhance LT patient survivals, refine selection criteria, establish new priority metrics, develop innovative bridging and downstaging strategies, and formulate redesigned LT strategies for HCC treatments.

Intestinal dysbiosis exacerbates susceptibility to the anti-NMDA receptor encephalitis-like phenotype by changing blood brain barrier permeability and immune homeostasis.

Changes in the intestinal microbiota have been observed in patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE). However, whether and how the intestinal microbiota is involved in the pathogenesis of NMDARE susceptibility needs to be demonstrated. Here, we first showed that germ-free (GF) mice that underwent fecal microbiota transplantation (FMT) from NMDARE patients, whose fecal microbiota exhibited low short-chain fatty acid content, decreased abundance of Lachnospiraceae, and increased abundance of Verrucomicrobiota, Akkermansia, Parabacteroides, Oscillospirales, showed significant behavioral deficits. Then, these FMT mice were actively immunized with an amino terminal domain peptide from the GluN1 subunit (GluN1356-385) to mimic the pathogenic process of NMDARE. We found that FMT mice showed an increased susceptibility to an encephalitis-like phenotype characterized by more clinical symptoms, greater pentazole (PTZ)-induced susceptibility to seizures, and higher levels of T2 weighted image (T2WI) hyperintensities following immunization. Furthermore, mice with dysbiotic microbiota had impaired blood-brain barrier integrity and a proinflammatory condition. In NMDARE-microbiota recipient mice, the levels of Evan's blue (EB) dye extravasation increased, ZO-1 and claudin-5 expression decreased, and the levels of proinflammatory cytokines (IL-1, IL-6, IL-17, TNF-α and LPS) increased. Finally, significant brain inflammation, mainly in hippocampal and cortical regions, with modest neuroinflammation, immune cell infiltration, and reduced expression of NMDA receptors were observed in NMDARE microbiota recipient mice following immunization. Overall, our findings demonstrated that intestinal dysbiosis increased NMDARE susceptibility, suggesting a new target for limiting the occurrence of the severe phenotype of NMDARE.

Pomegranate juice-containing serum inhibits migration of hepatocellular carcinoma cells and promotes apoptosis by induction of mitochondrial dysfunction.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, with an insidious onset and poor prognosis. Pomegranate is a fruit rich in many natural products with anti-cancer potential; however, its direct biological effects are difficult to evaluate in vitro because of changes in its active components after absorption and metabolism. This study was conducted to prepare pomegranate juice-containing serum (PJ serum) by gavage of pomegranate juice (PJ) in rats and to collect serum. The aim was to investigate the components and the effects of PJ serum on HCC cells by serum pharmacology. 56 compounds were identified in the PJ serum, including 6 prototype components. PJ serum selectively inhibited HCC cells proliferation and migration, and it promoted apoptosis of HCC cells without affecting LO2 cells activity. Furthermore, PJ serum reduced the mitochondrial membrane potential and increased the calcium ion concentration in HCC cells. Mechanistically, PJ serum up-regulated the expression of the Bax family, Caspases and TIMP2/MMP2, and down-regulated the expression of MMP9. This study revealed that PJ serum inhibited HCC cell migration by regulating the TIMP2/MMP2 balance and MMP9 expression and promoted HCC cell apoptosis by inducing mitochondrial dysfunction and causing a Caspase cascade. The polyphenols and flavonoids in PJ may be important components responsible for its anti-HCC activity after metabolism.

Rosa Roxburghii Tratt Fruit Extract Prevents Dss-Induced Ulcerative Colitis in Mice by Modulating the Gut Microbiota and the IL-17 Signaling Pathway.

Ulcerative colitis (UC) is a non-specific inflammatory bowel illness characterized by intestinal mucosal barrier degradation, inflammation, oxidative damage, and gut microbiota imbalances. Rosa roxburghii Tratt Fruit extract (RRTE) was extracted from Rosa roxburghii Tratt fruit, exhibiting an excellent prevention effect against UC; RRTE could prevent the damage of DSS-induced human normal colonic epithelial (NCM 460) cells, especially in cell viability and morphology, and oxidative damage. Additionally, in UC mice, RRTE could limit the intestinal mucosal barrier by increasing the expression of intestinal tight junction proteins and mucin, reducing inflammation and oxidative damage in colon tissue. More importantly, RRTE can increase the abundance of beneficial bacteria to regulate gut microbiota such as Ruminococcus, Turicibacter, and Parabacteroides, and reduce the abundance of harmful bacteria such as Staphylococcus and Shigella. Furthermore, transcriptomics of colonic mucosal findings point out that the beneficial effect of RRTE on UC could be attributed to the modulation of inflammatory responses such as the IL-17 and TNF signaling pathways. The qPCR results confirm that RRTE did involve the regulation of several genes in the IL-17 signaling pathway. In conclusion, RRTE could prevent DSS-induced damage both in vitro and in vivo.

Effects of Rosa roxburghii Tratt on Ulcerative Colitis: An Integrated Analysis of Network Pharmacology and Experimental Validation.

Rosa roxburghii Tratt is a traditional Chinese plant that has been used to treat different inflammatory diseases. The purpose of this study was to investigate the mechanism of action of Rosa roxburghii Tratt extract (RRTE) against ulcerative colitis (UC) using network pharmacology and experimental validation. HPLC-Q/Orbitrap MS was used to rapidly identify the substances contained in RRTE after extracting the active components from the fruit. Then, network pharmacology combined with molecular docking was used to explore the critical target and potential mechanism of RRTE against UC using the active ingredients in RRTE as the research object. Data are presented in a visual manner. Finally, the pharmacological effects of RRTE in alleviating UC were further verified using a DSS-induced UC model of NCM460. The results showed that 25 components in RRTE were identified. A total of 250 targets of the active components and 5376 targets associated with UC were collected. Furthermore, a systematic analysis of the Protein-Protein Interaction (PPI) networks suggests that epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and serine/threonine kinase 1 (AKT1) are critical targets for RRTE in the treatment of UC. A comprehensive regulatory network analysis showed that RRTE alleviated UC through the EGFR-mediated PI3K/Akt pathway, and molecular docking showed that active components could strongly bind to EGFR, PIK3R1, and AKT1. In addition, RRTE alleviated dextran sulfate sodium salt (DSS)-induced cell injury and significantly decreased the protein expression levels of EGFR, PIK3R1, and p-AKT in NCM460 cells in vitro. Furthermore, RRTE significantly regulated the expression of the apoptosis-related proteins Apoptotic protease-activating factor 1 (Apaf1), cleaved caspase-3, B-cell lymphoma-2 (Bcl2), and Bcl2 associated X protein (Bax). In conclusion, the components of RRTE are complex, and RRTE can relieve UC through the EGFR-mediated PI3K/Akt pathway.

Efficacy of immunotherapy and prognosis in anti-LGI1 encephalitis patients: A meta-analysis.

OBJECTIVE: To assess the efficacy and safety of immunotherapy for LGI1 antibody encephalitis, and consider the predictors of poor outcomes following immunotherapy. METHODS: We searched PubMed and Embase for articles reporting the immunotherapy data of anti-LGI1 encephalitis patients. The proportions of patients with poor outcomes (modified Rankin Scale [mRS] score > 2) at 3 months, 12 months, and the last follow-up, as well as the odds ratio [OR] of predictors were pooled. RESULTS: The review included 162 articles with 1066 patients. The proportion of patients with poor functional outcomes was 21% at 3 months, 14% at 12 months, and 14% at the last follow-up after receiving immunotherapy. The proportion of patients with reported relapse was 16.6%. The mean duration from onset to the first relapse was 15.6 months. Predictors significantly associated with poor outcomes were age (increase of 1 year), the presence of cognitive impairment, and CSF LGI1 antibody positive. We did not find a statistically significant association between the worst mRS score in the acute phase, the presence of faciobrachial dystonic seizures (FBDS), days from symptom onset to immunotherapy, second-line treatment, maintenance immunotherapy, or follow-up time and outcomes. INTERPRETATION: Although most patients respond to immunotherapy, a minority of patients still have poor outcomes. Advanced age, cognitive impairment, and CSF LGI1 antibody positive are associated with an increased risk of poor outcomes. However, due to the insufficiency of the data, these conclusions need to be interpreted with caution.

Effect of acupuncture on episodic memory for amnesia-type mild cognitive impairment: study protocol of a multicenter, randomized, controlled trial.

BACKGROUND: Amnesic mild cognitive impairment (aMCI) is the main subtype of mild cognitive impairment (MCI) and has the highest risk of conversion to Alzheimer's disease (AD) among all MCI subtypes. Episodic memory impairment is the early cognitive impairment of aMCI, which has become an important target for AD prevention. Previous clinical evidence has shown that acupuncture can improve the cognitive ability of MCI patients. This experiment aimed to observe the efficacy and neural mechanism of TiaoshenYizhi acupuncture on the episodic memory of patients with aMCI. METHODS: In this multicenter, parallel-group, double-blind, randomized controlled trial, 360 aMCI participants will be recruited from six subcenters and randomly assigned to the acupuncture group, sham acupuncture group, and control group. The acupuncture group will receive TiaoshenYizhi (TSYZ) acupuncture, the sham acupuncture group will use streitberger sham acupuncture, and the control group will only receive free health education. Participants in the two acupuncture groups will receive real acupuncture treatment or placebo acupuncture three times per week, 24 sessions over 8 consecutive weeks. The primary outcome will be global cognitive ability. Secondary outcomes will be a specific cognitive domain, including episodic memory and execution ability, electroencephalogram, and functional magnetic resonance imaging data. Outcomes will be measured at baseline and the fourth and eighth weeks after randomization. Repeated measurement analysis of variance and a mixed linear model will be used to observe the intervention effect. DISCUSSION: The protocol will give a detailed procedure to the multicenter clinical trial to further evaluate the efficacy and neural mechanism of TiaoshenYizhi acupuncture on episodic memory in patients with aMCI. From this research, we expect to provide clinical evidence for early aMCI management. TRIAL REGISTRATION: http://www.chictr.org.cn/edit.aspx?pid=142612&htm=4 , identifier: ChiCTR2100054009.

Adsorption of Cd (II) by a novel living and non-living Cupriavidus necator GX_5: optimization, equilibrium and kinetic studies.

Biosorbents have been extensively studied for heavy metal adsorption due to their advantages of low cost and high efficiency. In the study, the living and non-living biomass of Cupriavidus necator GX_5 previously isolated were evaluated for their adsorption capacity and/or removal efficiency for Cd (II) through batch experiments, SEM and FT-IR investigations. The maximum removal efficiency rates for the live and dead biomass were 60.51% and 78.53%, respectively, at an optimum pH of 6, a dosage of 1 g/L and an initial Cd (II) concentration of 5 mg/L. The pseudo-second-order kinetic model was more suitable for fitting the experimental data, indicating that the rate-limiting step might be chemisorption. The Freundlich isotherm model fit better than the Langmuir isotherm model, implying that the adsorption process of both biosorbents was heterogeneous. FT-IR observation reflected that various functional groups were involved in Cd (II) adsorption: -OH, -NH, C=O, C-O and C-C groups for the living biomass and -OH, -NH, C-H, C = O, C-N and N-H groups for the dead biomass. Our results imply that non-living biosorbents have a higher capacity and stronger strength for absorbing Cd (II) than living biomass. Therefore, we suggest that dead GX_5 is a promising adsorbent and can be used in Cd (II)-contaminated environments.

Tetrahydroxy stilbene glycoside ameliorates neuroinflammation for Alzheimer's disease via cGAS-STING.

Alzheimer's disease (AD), also known as senile dementia, is the most common degenerative disease of the central nervous system. Neuroinflammation is currently believed to be a crucial factor in the progression of AD, while its exact mechanism remains unclear. In this study, we demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation. Treating with a natural active ingredient tetrahydroxy stilbene glucoside (TSG) from the Chinese herb Polygonum multiflorum that has been well known for its unique anti-aging effect, learning-memory ability of AD mice was distinctly improved. Meanwhile, it was observed that the expressions of serum inflammatory cytokines and the activation of microglia in cerebral cortex and hippocampus were suppressed after TSG treatment, which was probably attributable to the decrease of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) triggered immune response and NLRP3 inflammasome activation. Furthermore, cell culture experiments employing LPS combined with IFN-γ induced microglia activation showed that TSG reversed the polarization status of M1-type microglia to restore the quiescence, and cGAS-STING elevation was observed in the activated microglia and normalized by TSG incubation. In addition, TSG suppressed the production of inflammatory cytokines such as IL-1ß, IL-6, TNF-α, IFN-α and IFN-ß, as well as the expression of IFN regulatory proteins such as IFIT1 and IRF7 in the LPS/IFN-γ-stimulated inflammatory response in BV2 cell. Finally, it was also verified that TSG are, in part, through a cGAS-STING dependent pathway and triggered NLRP3 inflammasome activation to inhibit neuroinflammation through interfering with cGAS-STING inhibitors. Taken together, our findings highlight the health benefits of TSG and its potential application in preventing cognitive disorders by inhibiting neuroinflammation through cGAS-STING signaling pathway in AD.

Autoimmune encephalitis with mGluR5 antibodies: A case series from China and review of the literature.

Background: Only 15 patients of autoimmune encephalitis with metabotropic glutamate receptor 5 (mGluR5) antibodies have been reported worldwide since 2011, mostly from western countries. Patients with different genetic backgrounds are necessary to further clarify the clinical phenotype and prognosis of this rare disease. Objective: We initially describe a case series from China to confirm the previous findings, expand the clinical phenotype, and identify the prognostic factors of autoimmune encephalitis with mGluR5 antibodies. Methods: Observational data with follow-up were prospectively collected from autoimmune encephalitis patients with mGluR5 antibodies. Clinical information and outcomes on current and previously reported cases were combined and analyzed. Results: We identified five patients (median age 35 years); two were female. The main clinical manifestations were behavioral/personality changes (five of five, 100%) and cognitive disorders (four of five, 80%), accompanied with other neurologic symptoms. Hypoventilation occurred in two (40%) patients, which was life-threatening. One patient had meningoencephalitis, suggesting a new phenotype in anti-mGluR5 encephalitis. All patients received immunotherapy. At the last follow-up (median 18 months), two (40%) patients showed complete recovery, two (40%) patients showed partial recovery, and one (20%) patient died. One (20%) patient had multiple relapses. Together with the 15 previously reported cases, associated tumors occurred in seven of 12 (58%) Western patients vs. one of eight (13%) Chinese patients. Modified Rankin Scale (mRS) scores at the last follow-up (median 31 months) were available in 16 patients. Patients with bad outcomes (mRS > 2, n = 4) were more likely to have hypoventilation at onset and higher mRS scores at peak of the disease. Conclusions: In patients with different genetic background, as Chinese, the clinical phenotype of anti-mGluR5 encephalitis is similar. Fewer paraneoplastic cases were observed in Chinese patients. Most patients showed good responses to immunotherapy and cancer treatment. The clinical outcomes were favorable in most patients.

Limitations on knowledge of autoimmune encephalitis and barriers to its treatment among neurologists: a survey from western China.

BACKGROUND: Autoimmune encephalitis (AE) is a group of severe antibody-mediated brain diseases. The understanding of clinical management of AE has developed rapidly. However, the knowledge level of AE and barriers to effective treatment among neurologists remains unstudied. METHODS: We conducted a questionnaire survey among neurologist in western China on knowledge of AE, treatment practices, and perspectives on barriers to treatment. RESULTS: A total of 1113 neurologists were invited and 690 neurologists from 103 hospitals completed the questionnaire with a response rate of 61.9%. Respondents correctly answered 68.3% of medical questions about AE. Some respondents (12.4%) never assayed for diagnostic antibodies if patients had suspected AE. Half (52.3%) never prescribed immunosuppressants for AE patients, while another 7.6% did not know whether they should do so. Neurologists who never prescribed immunosuppressants were more likely to have less education, a less senior job title, and to practice in a smaller setting. Neurologists who did not know whether to prescribe immunosuppressants were associated with less AE knowledge. The most frequent barrier to treatment, according to respondents, was financial cost. Other barriers to treatment included patient refusal, insufficient AE knowledge, lack of access to AE guidelines, drugs or diagnostic test, etc. CONCLUSION: Neurologists in western China lack AE knowledge. Medical education around AE is urgent needed and should be more targeted to individuals with less educated level or working in non-academic hospitals. Policies should be developed to increase the availability of AE related antibody testing or drugs and reduce the economic burden of disease.

Effect of acupuncture on brain functional networks in patients with mild cognitive impairment: an activation likelihood estimation meta-analysis.

BACKGROUND: Prior research has shown that acupuncture, a traditional Chinese medical therapy, may have a certain therapeutic effect in patients with mild cognitive impairment (MCI). Furthermore, some studies have explored the effects of acupuncture on the brain functional networks of MCI patients to investigate the mechanism of action. Different studies have analysed the brain regions involved in acupuncture-induced changes, but (to our knowledge) these have not been summarized by a systematic review. METHODS: We searched PubMed, EMBASE, Cochrane Library, SinoMed, CNKI and other databases in Chinese and English to identify neuroimaging studies of acupuncture interventions in MCI patients. After two stages of literature screening, bias risk assessment and data extraction, brain regions with significant differences were input into GingerALE software. Based on the activation likelihood estimation algorithm, coordinate-based meta-analyses were conducted. RESULTS: The changes in functional activation of 95 different areas in 8 trials, including 212 MCI patients, were analysed. The three most commonly used traditional acupuncture point locations in acupuncture interventions for MCI were KI3 (Taixi), LR3 (Taichong) and LI4 (Hegu). The results of the ALE data analysis showed that, after acupuncture intervention, the degree of activation in the anterior cingulate, inferior frontal gyrus, medial frontal gyrus and cerebellar tonsil of MCI patients increased significantly. CONCLUSIONS: Acupuncture intervention for MCI appears to change the plasticity of brain function and improve the cognitive function of patients. Due to the small number and low quality of the included studies, the conclusion of this meta-analysis should be treated with caution. REGISTRATION: PROSPERO reference CRD42022301056 (http://www.crd.york.ac.uk/PROSPERO).