Long-term relapse-free survival enabled by integrating targeted antibacteria in antitumor treatment.

The role of tumor-resident intracellular microbiota (TRIM) in carcinogenesis has sparked enormous interest. Nevertheless, the impact of TRIM-targeted antibacteria on tumor inhibition and immune regulation in the tumor microenvironment (TME) remains unexplored. Herein, we report long-term relapse-free survival by coordinating antibacteria with antitumor treatment, addressing the aggravated immunosuppression and tumor overgrowth induced by TRIM using breast and prostate cancer models. Combining Ag+ release with a Fenton-like reaction and photothermal conversion, simultaneous bacteria killing and multimodal antitumor therapy are enabled by a single agent. Free of immune-stimulating drugs, the agent restores antitumor immune surveillance and activates immunological responses. Secondary inoculation and distal tumor analysis confirm lasting immunological memory and systemic immune responses. A relapse-free survival of >700 days is achieved. This work unravels the crucial role of TRIM-targeted antibacteria in tumor inhibition and unlocks an unconventional route for immune regulation in TME and a complete cure for cancer.

Adjuvant chemotherapy and survival outcomes in older women with HR+/HER2- breast cancer: a propensity score-matched retrospective cohort study using the SEER database.

OBJECTIVES: This study aimed to investigate the impact of adjuvant chemotherapy (ACT) on survival outcomes in older women with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC). DESIGN: A retrospective cohort study using data from the Surveillance, Epidemiology, and End Results database, which contains publicly available information from US cancer registries. SETTING AND PARTICIPANTS: The study included 45 762 older patients with BC aged over 65 years diagnosed between 2010 and 2015. METHODS: Patients were divided into two groups based on age: 65-79 years and ≥80 years. Propensity score matching (PSM) was employed to balance clinicopathological characteristics between patients who received ACT and those who did not. Data analysis used the χ2 test and Kaplan-Meier method, with a subgroup analysis conducted to identify potential beneficiaries of ACT. OUTCOME MEASURES: Overall survival (OS) and cancer-specific survival (CSS). RESULTS: Due to clinicopathological characteristic imbalances between patients with BC aged 65-79 years and those aged ≥80 years, PSM was used to categorise the population into two groups for analysis: the 65-79 years age group (n=38 128) and the ≥80 years age group (n=7634). Among patients aged 65-79 years, Kaplan-Meier analysis post-PSM indicated that ACT was effective in improving OS (p<0.05, HR=0.80, 95% CI 0.73 to 0.88), particularly in those with advanced disease stages, but did not show a significant benefit in CSS (p=0.09, HR=1.13, 95% CI 0.98 to 1.31). Conversely, for patients aged ≥80 years, ACT did not demonstrate any improvement in OS (p=0.79, HR=1.04, 95% CI 0.79 to 1.36) or CSS (p=0.09, HR=1.46, 95% CI 0.69 to 2.26) after matching. Subgroup analysis also revealed no positive impact on OS and CSS. CONCLUSIONS: Patients with HR+/HER2- BC ≥80 years of age may be considered exempt from ACT because no benefits were found in terms of OS and CSS.

Update on the STING Signaling Pathway in Developing Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with limited treatment options. Inflammation caused by metabolic disturbances plays a significant role in NAFLD development. Stimulator of interferon gene (STING), a critical regulator of innate immunity, induces the production of interferons and other pro-inflammatory factors by recognizing cytoplasmic DNA to defend against pathogen infection. The STING-mediated signaling pathway appears to play a vital role in hepatic inflammation, metabolic disorders, and even carcinogenesis. Promisingly, pharmacological interventions targeting STING have shown improvements in the pathological state of NAFLD. Macrophages, dendritic cells, natural killer cells, and T cell pathways regulated by STING present potential novel druggable targets for NAFLD treatment. Further research and development in this area may offer new therapeutic options for managing NAFLD effectively.

Strategies for promoting tendon-bone healing: Current status and prospects.

Tendon-bone insertion (TBI) injuries are common, primarily involving the rotator cuff (RC) and anterior cruciate ligament (ACL). At present, repair surgery and reconstructive surgery are the main treatments, and the main factor determining the curative effect of surgery is postoperative tendon-bone healing, which requires the stable combination of the transplanted tendon and the bone tunnel to ensure the stability of the joint. Fibrocartilage and bone formation are the main physiological processes in the bone marrow tract. Therefore, therapeutic measures conducive to these processes are likely to be applied clinically to promote tendon-bone healing. In recent years, biomaterials and compounds, stem cells, cell factors, platelet-rich plasma, exosomes, physical therapy, and other technologies have been widely used in the study of promoting tendon-bone healing. This review provides a comprehensive summary of strategies used to promote tendon-bone healing and analyses relevant preclinical and clinical studies. The potential application value of these strategies in promoting tendon-bone healing was also discussed.

The prognostic role of lymph node ratio in breast cancer patients received neoadjuvant chemotherapy: A dose-response meta-analysis.

Background: As neoadjuvant chemotherapy is widely used in breast cancer patients, the lymph node ratio has not been fully validated as a prognostic indicator of breast cancer received neoadjuvant chemotherapy. This study was conducted to investigate the prognostic value of lymph node ratio in breast cancer patients received neoadjuvant chemotherapy. Methods: Systematic searches were performed in the PubMed, Embase, and Cochrane Library databases until 15 December 2021 for studies on the association between lymph node ratio and the prognosis of breast cancer after neoadjuvant chemotherapy. Overall survival and disease-free survival were used as outcome events, and hazard ratio was chosen as the parameter to evaluate the correlation. The dose-response relationship was assessed by restricted cubic splines. In the subgroup analyses, which were used to explore potential heterogeneity among the included studies according to study region and sample size. Sensitivity analysis was performed to assess the stability of individual studies, and publication bias was determined with funnel plots, Begg's test, and Egger's test. All statistical analyses were performed using Stata 15.1. Results: A total of 12 studies with 4,864 patients were included in this meta-analysis. In this study, high lymph node ratio was significantly associated with decreased overall survival (HR: 4.74; 95%CI: 3.36-6.67; P < 0.001) and disease-free survival (HR: 4.77; 95%CI: 3.69-6.17; P < 0.001). Moreover, the dose-response meta-analysis showed a linear association between higher lymph node ratio and shorter overall survival and disease-free survival in breast cancer patients after neoadjuvant chemotherapy. Conclusions: The meta-analysis suggested that high lymph node ratio was significantly associated with short overall survival and disease-free survival in breast cancer patients after neoadjuvant chemotherapy. Therefore, lymph node ratio is an independent predictive factor for the prognosis of breast cancer patients after neoadjuvant chemotherapy, which may better refine the cancer staging system.

Prenatal exposure to organochlorine pesticides and infant growth: A longitudinal study.

BACKGROUND: The association between exposure to organochlorine pesticides (OCPs) and infant growth has been reported contradictorily in previous studies. Few studies have investigated the effects of prenatal exposure to OCPs on infant growth assessed longitudinally at multiple time points. OBJECTIVES: The purpose of the study was to examine the associations between prenatal exposure to OCPs and infant growth at birth, 6, 12 and 24 months of age, and further to explore the potential sex-specific effects. METHODS: The study population included 1039 mother-infant pairs who participated in a birth cohort study in Wuhan, China. The weight, length and body mass index (BMI) z-score of infants were measured and calculated at birth, 6, 12 and 24 months of age. The overweight status was defined as BMI z-score ≥ 85th percentile according to the standard of World Health Organization. The concentrations of OCPs were measured in cord serum, including hexachlorocyclohexanes (HCHs, consisted of α-HCH, ß-HCH, and γ-HCH), p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) and its metabolites: p,p'-dichlorodiphenyldichloroethane (p,p'-DDD), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE). Generalized linear models were applied to estimate the associations of cord OCPs with infant growth parameters. A group-based semiparametric mixture model was used to estimate growth patterns of infants. Linear-mixed growth curve models were used to examine relationships between predicted growth trajectories and prenatal exposure to OCPs. Weighted quantile sum regression (WQSR) analyses were used to estimate the mixture effects of OCPs on infant growth. RESULTS: Higher cord serum ß-HCH concentrations were associated with higher BMI z-score at 12 [ß = 0.07, 95%CI: 0.01, 0.13] and 24 months of age [ß = 0.08, 95% CI: 0.02, 0.14]. Similar patterns were observed for relationships of γ-HCH [ß = 0.04, 95%CI: 0.01, 0.07] and p,p'-DDT [ß = 0.03, 95% CI: 0.00, 0.06] with BMI z-score at 6 and 12 months of age, respectively. However, higher cord serum p,p'-DDE concentrations were associated with a reduction of BMI z-score at 6 months of age [ß = -0.07, 95% CI: -0.12, -0.01]. Cord serum ß-HCH was also positively associated with the risk of overweight at 12 months of age [RR = 1.16, 95% CI (1.02, 1.33), for the medium vs the lowest tertile]. Among girls, the effects of ß-HCH on BMI z-score and overweight status were stronger than boys at 12 and 24 months of age. No statistically significant relationships of other OCPs with infant growth were observed. CONCLUSIONS: Prenatal exposure to ß-HCH was associated with increased BMI z-score and higher risk of overweight status in infants especially at 12 and 24 months of age, which seemed to be stronger in girls.

Prevalence and associated factors of antenatal depression: Systematic reviews and meta-analyses.

To evaluate the global prevalence of antenatal depression and clarify its potential associated factors, we conducted two systematic reviews and meta-analyses, where appropriate. PubMed, Web of Science, and Embase were used to identify studies published up to Feb 28, 2019. The pooled prevalence of any antenatal depression across 173 studies with 182 reports was 20.7% (95% CI 19.4-21.9%, P = 0.000, I2 = 98.4%), and the pooled prevalence of major antenatal depression across 72 studies with 79 reports was 15.0% (95% CI 13.6-16.3%, P = 0.000, I2 = 97.8%). The prevalence of antenatal depression was higher in low- or lower-middle-income countries, and in studies using self-report instruments or conducted after the year 2010. History of depression, lack of social support, single/separated/divorced status, unplanned pregnancy, unemployment, experience of violence, and smoking before or during pregnancy were significantly associated with antenatal depression. The results of our study indicated that a significant number of pregnant women experience depression and verified some factors that are related to this disorder. As countermeasures, it is important to develop effective risk assessment strategies as well as prevention and intervention strategies for antenatal depression based on its associated factors.

Design, synthesis and biological evaluation of 3-nitro-1,8-naphthalimides as potential antitumor agents.

A series of 3-nitro-naphthalimides 1(1a-1h) were designed and synthesized as antitumor agents. MTT assay results showed that all these compounds exhibited obvious antiproliferative activity against SKOV3, HepG2, A549, T-24 and SMMC-7721 cancer cell lines, while compound 1a displayed the best antiproliferative activity against HepG2 and T-24 cell lines in comparison with mitonafide, with IC50 of 9.2 ± 1.8 and 4.133 ± 0.9 µM, respectively. In vivo antiproliferative activity assay results showed that compound 1a exhibited good antiproliferative activity in the HepG2 and T-24 models, compared with mitonafide. Action mechanism results showed that compound 1a could induced the damage of DNA and the inhibition topo I, accompanying by inducing the G2-stage arresting and the apoptosis of T-24 cancer cells through up-regulating expression levels of cyclin B1, cdc 2-pTy, Wee1, γH2AX, p21, Bax and cytochrome c and down-regulating expression of Bcl-2.

Carbon dots-fed Shewanella oneidensis MR-1 for bioelectricity enhancement.

Bioelectricity generation, by Shewanella oneidensis (S. oneidensis) MR-1, has become particularly alluring, thanks to its extraordinary prospects for energy production, pollution treatment, and biosynthesis. Attempts to improve its technological output by modification of S. oneidensis MR-1 remains complicated, expensive and inefficient. Herein, we report on the augmentation of S. oneidensis MR-1 with carbon dots (CDs). The CDs-fed cells show accelerated extracellular electron transfer and metabolic rate, with increased intracellular charge, higher adenosine triphosphate level, quicker substrate consumption and more abundant extracellular secretion. Meanwhile, the CDs promote cellular adhesion, electronegativity, and biofilm formation. In bioelectrical systems the CDs-fed cells increase the maximum current value, 7.34 fold, and power output, 6.46 fold. The enhancement efficacy is found to be strongly dependent on the surface charge of the CDs. This work demonstrates a simple, cost-effective and efficient route to improve bioelectricity generation of S. oneidensis MR-1, holding promise in all relevant technologies.

Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives as antitumor agents: in vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response.

A series of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives (3a1-3d6) were designed and synthesized as antitumor agents. In vitro antitumor assay results showed that some compounds exhibited moderate to high inhibitory activities against HepG2, SK-OV-3, NCI-H460 and BEL-7404 tumor cell lines, and most compounds exhibited much lower cytotoxicities against HL-7702 normal cell line compared to 5-FU and cisplatin. In vivo antitumor assay results showed that the representative compound 3a1 exhibited effective inhibition on tumor growth in the HepG2 xenograft mouse model. Mechanistic studies suggested that 3a1 may exert antitumor activity by the up-regulation of Bax, intracellular Ca2+ release, ROS generation, p21, p27 and p53, downregulation of Bcl-2, activation of caspase-9 and caspase-3 and subsequent cleavage of PARP, and inhibition of CDK activity.

Design and mechanism of core-shell TiO2 nanoparticles as a high-performance photothermal agent.

Photothermal agents (PTAs) with high biocompatibility and therapeutic efficacy have become particularly fascinating, however, knowledge of their photothermal performance is rather limited. Herein, rationally designed core-shell TiO2 nanoparticles have been fabricated using a mild hydrogenation method, where NaBH4 was used as the H2 source. The resultant TiO2 possesses strong optical absorption in the NIR region and remarkable photothermal conversion capability and stability, leading to a high inhibition rate on cancer cells. In particular, its photothermal conversion efficiency is as high as 55.2%, which is 204% that of the fully hydrogenated amorphous TiO2. More importantly, the underlying mechanism is proposed. It is revealed that while the oxygen vacancies induced by the hydrogenation can introduce defect levels in the band gap and enhance the optical absorption, the superfluous oxygen vacancies and defects reduce the photothermal conversion capability and thermal conductivity to a large extent. Controlling the hydrogenation degree and maintaining a certain extent of crystallization are, therefore, crucial to the photothermal properties. This new understanding of the photothermal conversion mechanism may have provided a fresh route to design and optimize PTAs and inspire considerable interest to turn a large variety of semiconductor metal oxides into competent PTAs by appropriate hydrogenation.

Does Arthroplasty Provide Better Outcomes Than Internal Fixation At Mid- and Long-term Followup? A Meta-analysis.

BACKGROUND: Arthroplasty has been shown to be superior regarding low risk of reoperation and better function score to internal fixation for treatment of displaced femoral neck fractures at short-term followup. However, there are unanswered questions regarding the efficacy of arthroplasty in the longer term compared with internal fixation. QUESTIONS/PURPOSES: We performed a meta-analysis comparing arthroplasty (hemiarthroplasty or THA) with internal fixation in patients with displaced femoral neck fractures with respect to (1) mortality, (2) reoperation, (3) functional recovery, and (4) complications, including only randomized trials with a minimum of 4 years followup. METHODS: Computerized databases, including PubMed (MEDLINE), EMBASE, Cochrane Register of Controlled Trials databases, and Web of Science™ were searched for studies published from the inception date for each database to March 2014. Eleven randomized controlled trials that compared arthroplasty (either hemiarthroplasty or THA) with internal fixation for treatment of patients with a femoral neck fracture were included in our analysis. The quality of the trials was assessed according to the Cochrane Handbook and meta-analyses were conducted using RevMan 5.2 software from the Cochrane Collaboration. The heterogeneity among studies was evaluated by the I-squared index (I2) and publication bias was assessed using forest plots. RESULTS: There were no differences between the internal fixation and arthroplasty groups for patient mortality at mid-term (48.4% vs 46.8%) or long-term followup (83.2% vs 81.5%). Arthroplasty was associated with a lower risk of reoperation at mid-term (7.2% vs 39.8%; relative risk [RR]=0.10; 95% CI, 0.06-0.07) and at long-term followup (14.3% vs 43.8%; RR=0.10; 95% CI, 0.06-0.07). Arthroplasty was associated with better functional recovery at mid-term followup (standard mean difference [SMD]=0.55; 95% CI, 0.02-1.09), whereas function at long-term followup (SMD=0.14; 95% CI, -0.35 to 0.62) was not different between the arthroplasty and internal fixation groups. There were no significant differences in subsequent ipsilateral fractures (1.5% vs 1.2%; RR=2.18; 95% CI, 0.32-14.67; p=0.42) and deep infections (2.7% vs 2.9%; RR=0.89; 95% CI, 0.40-2.01; p=0.78) between patients treated with arthroplasty and internal fixation. CONCLUSIONS: Based on our results, we found that compared with internal fixation, arthroplasty may result in a lower rate of subsequent reoperation at mid- and long-term followup, and better mid-term functional recovery. Future studies should investigate the mid- and long-term results of THAs compared with hemiarthroplasty.

Oxymatrine protects rat brains against permanent focal ischemia and downregulates NF-kappaB expression.

BACKGROUND: Oxymatrine is proven to protect ischemic and reperfusion injury in liver, intestine and heart, this effect is via anti-inflammation and anti-apoptosis. Whether this protective effect applies to ischemic injury in brain, we therefore investigate the potential neuroprotective role of oxymatrine and the underlying mechanisms. METHODS: Male, Sprague-Dawley rats were randomly assigned to four groups: permanent middle cerebral artery occlusion (pMCAO), high dose (pMCAO+oxymatrine 120 mg/kg), low dose (pMCAO+oxymatrine 60 mg/kg) and sham operated group. We used a permanent middle cerebral artery occlusion model and administered oxymatrine intraperitoneally immediately after cerebral ischemia and once daily on the following days. At 24 h after MCAO, neurological deficit was evaluated using a modified six point scale; brain water content was measured; NF-kappaB expression was measured by immunohistochemistry, Western blotting and RT-PCR. Infarct volume was analyzed with 2, 3, 5-triphenyltetrazolium chloride (TTC) staining at 72 h. RESULTS: Compared with pMCAO group, neurological deficit in high dose group was improved (P<0.05), infarct volume was decreased (P<0.001) and cerebral edema was alleviated (P<0.05). Consistent with these indices, immunohistochemistry, Western blot and RT-PCR analysis indicated that NF-kappaB expression was significantly decreased in high dose group. Low dose of oxymatrine did not affect NF-kappaB expression in pMCAO rats. CONCLUSIONS: Oxymatrine reduced infarct volume induced by pMCAO, this effect may be through the decreasing of NF-kappaB expression.