Radiotherapy is one of the most common countermeasures for treating a wide range of tumors. However, the radioresistance of cancer cells is still a major limitation for radiotherapy applications. Efforts are continuously ongoing to explore sensitizing targets and develop radiosensitizers for improving the outcomes of radiotherapy. DNA double-strand breaks are the most lethal lesions induced by ionizing radiation and can trigger a series of cellular DNA damage responses (DDRs), including those helping cells recover from radiation injuries, such as the activation of DNA damage sensing and early transduction pathways, cell cycle arrest, and DNA repair. Obviously, these protective DDRs confer tumor radioresistance. Targeting DDR signaling pathways has become an attractive strategy for overcoming tumor radioresistance, and some important advances and breakthroughs have already been achieved in recent years. On the basis of comprehensively reviewing the DDR signal pathways, we provide an update on the novel and promising druggable targets emerging from DDR pathways that can be exploited for radiosensitization. We further discuss recent advances identified from preclinical studies, current clinical trials, and clinical application of chemical inhibitors targeting key DDR proteins, including DNA-PKcs (DNA-dependent protein kinase, catalytic subunit), ATM/ATR (ataxia-telangiectasia mutated and Rad3-related), the MRN (MRE11-RAD50-NBS1) complex, the PARP (poly[ADP-ribose] polymerase) family, MDC1, Wee1, LIG4 (ligase IV), CDK1, BRCA1 (BRCA1 C terminal), CHK1, and HIF-1 (hypoxia-inducible factor-1). Challenges for ionizing radiation-induced signal transduction and targeted therapy are also discussed based on recent achievements in the biological field of radiotherapy.

It has been reported that gut probiotics play a major role in the bidirectional communication between the gut and the brain. Probiotics may be essential to people with depression, which remains a global health challenge, as depression is a metabolic brain disorder. However, the efficacy of probiotics for depression is controversial. This study aimed to systematically review the existing evidence on the effect of probiotics-based interventions on depression. Randomized, controlled trials, identified through screening multiple databases and grey literature, were included in the meta-analysis. The meta-analysis was performed using Review Manager 5.3 software using a fixed-effects model. The meta-analysis showed that probiotics significantly decreased the depression scale score (MD (depressive disorder) = −0.30, 95% CI (−0.51–−0.09), p = 0.005) in the subjects. Probiotics had an effect on both the healthy population (MD = −0.25, 95% CI (−0.47–−0.03), p = 0.03) and patients with major depressive disorder (MDD) (MD = −0.73, 95% CI (−1.37–−0.09), p = 0.03). Probiotics had an effect on the population aged under 60 (MD = −0.43, 95% CI (−0.72–−0.13), p = 0.005), while it had no effect on people aged over 65 (MD = −0.18, 95% CI (−0.47–0.11), p = 0.22). This is the first systematic review and meta-analysis with the goal of determining the effect of probiotics on depression. We found that probiotics were associated with a significant reduction in depression, underscoring the need for additional research on this potential preventive strategy for depression.

Genomic instability is the hallmark of various cancers with the increasing accumulation of DNA damage. The application of radiotherapy and chemotherapy in cancer treatment is typically based on this property of cancers. However, the adverse effects including normal tissues injury are also accompanied by the radiotherapy and chemotherapy. Targeted cancer therapy has the potential to suppress cancer cells’ DNA damage response through tailoring therapy to cancer patients lacking specific DNA damage response functions. Obviously, understanding the broader role of DNA damage repair in cancers has became a basic and attractive strategy for targeted cancer therapy, in particular, raising novel hypothesis or theory in this field on the basis of previous scientists’ findings would be important for future promising druggable emerging targets. In this review, we first illustrate the timeline steps for the understanding the roles of DNA damage repair in the promotion of cancer and cancer therapy developed, then we summarize the mechanisms regarding DNA damage repair associated with targeted cancer therapy, highlighting the specific proteins behind targeting DNA damage repair that initiate functioning abnormally duo to extrinsic harm by environmental DNA damage factors, also, the DNA damage baseline drift leads to the harmful intrinsic targeted cancer therapy. In addition, clinical therapeutic drugs for DNA damage and repair including therapeutic effects, as well as the strategy and scheme of relative clinical trials were intensive discussed. Based on this background, we suggest two hypotheses, namely “environmental gear selection” to describe DNA damage repair pathway evolution, and “DNA damage baseline drift”, which may play a magnified role in mediating repair during cancer treatment. This two new hypothesis would shed new light on targeted cancer therapy, provide a much better or more comprehensive holistic view and also promote the development of new research direction and new overcoming strategies for patients.

Objective: Atopic dermatitis (AD) is a prevalent, burdensome, and psychologically important pediatric concern. Probiotics have been suggested as a treatment for AD. Some reports have explored this topic; however, the utility of probiotics for AD remains to be firmly established.Methods: To assess the effects of probiotics on AD in children, the PubMed/Medline, Cochrane Library Scopus, and OVID databases were searched for reports published in the English language.Results: Thirteen studies were identified. Significantly higher SCORAD values favoring probiotics over controls were observed (mean difference [MD], −3.07; 95% confidence interval [CI], −6.12 to −0.03; P < 0.001). The reported efficacy of probiotics in children < 1 year old was −1.03 (95%CI, −7.05 to 4.99) and that in children 1–18 years old was −4.50 (95%CI, −7.45 to −1.54; P < 0.001). Subgroup analyses showed that in Europe, SCORAD revealed no effect of probiotics, whereas significantly lower SCORAD values were reported in Asia (MD, −5.39; 95%CI, −8.91 to −1.87). Lactobacillus rhamnosus GG (MD, 3.29; 95%CI, −0.30 to 6.88; P = 0.07) and Lactobacillus plantarum (MD, −0.70; 95%CI, −2.30 to 0.90; P = 0.39) showed no significant effect on SCORAD values in children with AD. However, Lactobacillus fermentum (MD, −11.42; 95%CI, −13.81 to −9.04), Lactobacillus salivarius (MD, −7.21; 95%CI, −9.63 to −4.78), and a mixture of different strains (MD, −3.52; 95%CI, −5.61 to −1.44) showed significant effects on SCORAD values in children with AD.Conclusions: Our meta-analysis indicated that the research to date has not robustly shown that probiotics are beneficial for children with AD. However, caution is needed when generalizing our results, as the populations evaluated were heterogeneous. Randomized controlled trials with larger samples and greater power are necessary to identify the species, dose, and treatment duration of probiotics that are most efficacious for treating AD in children.

We studied Cd, Cr, As, Ni, Mn, Pb, and Hg in three agricultural areas of Hunan province and determined the potential non-carcinogenic and carcinogenic risks for residents. Soil and brown rice samples from Shimen, Fenghuang, and Xiangtan counties were analyzed by atomic absorption spectroscopy. Soil levels of Cd and Hg were greatest, followed by As and Ni. The mean concentrations of heavy metals in brown rice were Cd 0.325, Cr 0.109, As 0.344, Ni 0.610, Mn 9.03, Pb 0.023, and Hg 0.071 mg/kg, respectively. Cd and Hg had greater transfer ability from soil to rice than the other elements. Daily intake of heavy metals through brown rice consumption were estimated to be Cd 2.30, Cr 0.775, As 2.45, Ni 4.32, Pb 0.162, Mn 64.6 and Hg 0.503 µg/(kg·day), respectively. Cd, Hg and As Hazard Quotient values were greater than 1 and Cd, Cr, As and Ni Cancer Risk values were all greater than 10−4. The total non-carcinogenic risk factor was 14.6 and the total carcinogenic risk factor was 0.0423. Long-term exposure to heavy metals through brown rice consumption poses both potential non-carcinogenic and carcinogenic health risks to the local residents.