Perspective in the Mechanisms for Repairing Sperm DNA Damage.

DNA damage in spermatozoa is a major cause of male infertility. It is also associated with adverse reproductive outcomes (including reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage). The damage to sperm DNA occurs during the production and maturation of spermatozoa, as well as during their transit through the male reproductive tract. DNA damage repair typically occurs during spermatogenesis, oocytes after fertilization, and early embryonic development stages. The known mechanisms of sperm DNA repair mainly include nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR), and double-strand break repair (DSBR). The most severe type of sperm DNA damage is double-strand break, and it will be repaired by DSBR, including homologous recombination (HR), classical non-homologous end joining (cNHEJ), alternative end joining (aEJ), and single-strand annealing (SSA). However, the precise mechanisms of DNA repair in spermatozoa remain incompletely understood. DNA repair-associated proteins are of great value in the repair of sperm DNA. Several repair-related proteins have been identified as playing critical roles in condensing chromatin, regulating transcription, repairing DNA damage, and regulating the cell cycle. It is noteworthy that XRCC4-like factor (XLF) and paralog of XRCC4 and XLF (PAXX) -mediated dimerization promote the processing of populated ends for cNHEJ repair, which suggests that XLF and PAXX have potential value in the mechanism of sperm DNA repair. This review summarizes the classic and potential repair mechanisms of sperm DNA damage, aiming to provide a perspective for further research on DNA damage repair mechanisms.

Lapagyl mitigates UV-induced inflammation and immunosuppression via Foxp3+ Tregs and CCL pathway: A single-cell transcriptomics study.

BACKGROUND: As the largest organ of the body, the skin is constantly subjected to ultraviolet radiation (UVR), leading to inflammations and changes that mirror those seen in chronological aging. Although various small molecule drugs have been explored for treating skin photoaging, they typically suffer from low stability and a high incidence of adverse reactions. Consequently, the continued investigation of photoaging treatments, particularly those utilizing herbal products, remains a critical clinical endeavor. One such herbal product, Lapagyl, is derived from the bark of the lapacho tree and possesses antioxidant efficacies that could be beneficial in combating skin photoaging. PURPOSE: This research aimed to evaluate the efficacy of the herbal product Lapagyl in combating UVR-induced skin photoaging. Additionally, it sought to unravel the mechanisms by which Lapagyl promotes the regeneration of the skin extracellular matrix. METHODS: To investigate whether Lapagyl can alleviate skin aging and damage, a UVR radiation model was established using SKH-1 hairless mice. The dorsal skins of these mice were evaluated for wrinkle formation, texture, moisture, transepidermal water loss (TEWL), and elasticity. Pathological assessments were conducted to determine Lapagyl's efficacy. Additionally, single-cell sequencing and spectrum analysis were employed to elucidate the working mechanisms and primary components of Lapagyl in addressing UVR-induced skin aging and injury. RESULTS: Lapagyl markedly reduced UVR-induced wrinkles, moisture loss, and elasticity decrease in SKH-1 mice. Single-cell sequencing demonstrated that Lapagyl corrected the imbalance in cell proportions caused by UVR, decreased UVR-induced ROS expression, and protected basal and spinous cells from skin damage. Additionally, Lapagyl effectively prevented the entry of inflammatory cells into the skin by reducing CCL8 expression and curtailed the UVR-induced formation of Foxp3+ regulatory T cells (Tregs) in the skin. Both pathological assessments and ex vivo skin model results demonstrated that Lapagyl effectively reduced UVR-induced damage to collagen and elastin. Spectrum analysis identified Salidroside as the primary compound remaining in the skin following Lapagyl treatment. Taken together, our study elucidated the skin protection mechanism of the herbal product Lapagyl against UVR damage at the cellular level, revealing its immunomodulatory effects, with salidroside identified as the primary active compound for skin. CONCLUSION: Our study provided a thorough evaluation of Lapagyl's protective effects on skin against UVR damage, delving into the mechanisms at the cellular level. We discovered that Lapagyl mitigates skin inflammation and immunosuppression by regulating Foxp3+ Tregs and the CCL pathway. These insights indicate that Lapagyl has potential as a novel therapeutic option for addressing skin photoaging.

Establishment and application of perceived age prediction model for the periocular aging research of Chinese Han women.

BACKGROUND: The assessment of skin aging through skin measurements faces limitations, making perceived age evaluation a more valuable and direct tool for assessing skin aging. Given that the aging process markedly affects the appearance of the eye contour, characterizing the eye region could be beneficial for perceived age assessment. This study aimed to analyze age-correlated changes in the eye contour within the Chinese Han female population and to develop, validate, and apply a multiple linear regression model for predicting perceived age. MATERIALS AND METHODS: A naïve panel of 107 Chinese women assessed the perceived ages of 212 Chinese Han women. Instrumental analysis evaluated periorbital parameters, including palpebral fissure width (PFW), palpebral fissure height (PFH), acclivity of palpebral fissure (AX), angle of inner canthal (AEN), and angle of outer canthal (AEX). These parameters were used to construct a multiple linear regression model for predicting the perceived ages of Chinese Han women. A combined treatment using Fotona 4D and an anti-aging eye cream, formulated with plant extracts, peptides, and antioxidants, was conducted to verify the cream's anti-aging efficacy and safety. This eye cream was then tested in a large-scale clinical trial involving 101 participants. The prediction model was employed in this trial to assess the perceived ages of the women after an 8-week application of the eye cream. RESULTS: All parameters were observed to decrease with age. An intergroup comparison indicated that eyelid aging in Chinese Han women accelerates beyond the age of 50. Consequently, a linear regression model was constructed and validated, with the perceived age being calculated as 183.159 - 1.078 * AEN - 4.487 * PFW + 6.061 * PFH - 1.003 * AX - 0.328 * AEX. The anti-aging efficacy and safety of the eye cream were confirmed through combined treatment with Fotona 4D, showing improvements in wrinkles, elasticity, and dark circles under the eyes. In a large-scale clinical evaluation using this eye cream, a perceived age prediction model was applied, suggesting that 8 weeks of use made participants appear 2.25 years younger. CONCLUSION: Our study developed and validated a multiple linear regression model to predict the perceived age of Chinese Han women. This model was successfully utilized in a large-scale clinical evaluation of anti-aging eye cream, revealing that 8 weeks of usage made participants appear 2.25 years younger. This method effectively bridges the gap between clinical research and consumer perceptions, explores the complex factors influencing perceived age, and aims to improve anti-aging formulations.

Combination of dimethylmethoxy chromanol and turmeric root extract synergically attenuates ultraviolet-induced oxidative damage by increasing endogenous antioxidants in HaCaT cells.

BACKGROUND: Repeated exposure to UV generates excessive reactive oxygen species (ROS) and damages the enzymatic antioxidant defense system including quinone oxidoreductase 1 (NQO1) and superoxide dismutase (SOD) in skin. Topical application of antioxidants may prevent the undesired damage of cellular proteins, lipids and DNA in skin. Dimethylmethoxy chromanol (DMC) is a bioinspired molecule, designed to be a structural analog to the γ-tocopherol that is naturally present in vegetables and plants. Turmeric root extract (TRE) is from a plant in South Asia extensively used as a food spice & vegetable, and its main components are turmerones. As both DMC and TRE are strong antioxidants with complementary antioxidation mechanisms, the aim of this study was to investigate the enhanced protective effects of their combination on oxidative damage in HaCaT cells following UVB exposure. MATERIALS AND METHODS: The effects of single and combined administrations of DMC and TRE on the SOD activity of HaCaT cells were evaluated by the SOD assay and qPCR. The NQO1 expression in the UVB-treated HaCaT cells was analyzed by the Western Blot. Furthermore, a clinical test involving 24 subjects was conducted to evaluate the in vivo antioxidation efficacies of the serum formulated with the combination of DMC and TRE at the optimal weight ratio. RESULTS: SOD assay showed that pretreating DMC or TRE alone could not preserve the impaired HaCaT SOD activity after UVB treatment. DMC and TRE at 1:1 weight ratio was the optimal combination to enhance the HaCaT SOD activity by approximately more than 1-fold compared with either of the single treated groups. No enhancement effect was observed at other mixing ratios. The 1:1 weight ratio was further proved to be optimal as this combination boosted the NQO1 expression by more than 50%, whereas no boosting effect was observed at other mixing ratios. The clinical test of the serum containing this optimal antioxidant combination demonstrated promising in vivo antioxidation efficacies after 4-week use, including 7.16% improvement in skin lightening, 18.29% reduction in skin redness, 35.68% decrease in TEWL, 19.05% increase in skin gloss and 32.04% enhancement in skin firmness. CONCLUSION: Collectively, our results indicated that the combination of DMC and TRE at 1:1 weight ratio attenuated the UV-induced oxidative damage by synergistically boosting endogenous antioxidant enzyme activity in HaCaT cells. Therefore, this optimal antioxidant combination is a promising treatment to boost skin antioxidation defense system.

Association of probiotic ingestion with serum sex steroid hormones among pre- and postmenopausal women from the NHANES, 2013-2016.

BACKGROUND: Sex hormone-related diseases, encompassing a wide range of conditions from reproductive disorders to certain cancers, pose significant health challenges worldwide. Recent scientific investigations have highlighted the intricate interplay between the gut microbiome and sex hormone regulation, indicating the potential for microbiota-targeted interventions in the management of such diseases. Although individual studies have elucidated the influence of the gut microbiome on sex hormones, a comprehensive cross-sectional examination of the population-wide prevalence of probiotic intake and its correlation with sex hormones is still lacking. OBJECTIVES: This study aimed to evaluate the association of probiotic ingestion with sex hormones in pre- and post-menopausal women. METHODS: We conducted an observational cohort study comprising a nationally representative sample of adults who participated in the National Health and Nutrition Examination Survey between 2013 and 2016. Probiotic ingestion was considered when a subject reported yogurt or probiotic supplement consumption during the 24-h dietary recall or during the Dietary Supplement Use 30-Day questionnaire. A survey-weighted generalized linear model was used to analyze the association between probiotic intake and female/male sex hormones. To reduce selection bias, we used propensity score matching (PSM). RESULTS: This study included 2,699 women, with 537 of them consuming yogurt and/or dietary supplements containing probiotics, while the remaining 2,162 women did not consume any probiotics. The findings indicated that there were associations between probiotic intake and sex hormone levels in premenopausal and postmenopausal women. For premenopausal women, probiotic intake was positively associated with estradiol (E2) levels. On the contrary, in postmenopausal women, probiotic intake was inversely associated with total testosterone (TT) levels. CONCLUSIONS: This study indicated that probiotic consumption was associated with higher E2 level in premenopausal women and lower TT level in postmenopausal women. Probiotic intake might be a sensible strategy for preventing sex hormone-related diseases.

Heavy metal fraction, pollution, and source-oriented risk assessment in biofilms on a river system polluted by mining activities.

The Lanping Pb-Zn mine is the largest source of Pb and Zn ores in China, thus posing a great threat to local ecosystems and human health. A total of seven heavy metals (Zn, Pb, Ni, Cu, Cr, Cd, and As) in the Bijiang River near the Pb-Zn mine were measured in winter and summer to assess their spatial-temporal enrichment, ecological risk, and source-oriented health risk in periphytic biofilms. Positive matrix factorization (PMF) receptor model and clustering analysis were used to quantitatively identify pollution sources. The results of PMF were then imported into the health risk assessment to further determine the carcinogenic and noncarcinogenic risks of various pollution sources. The results indicated distinct seasonal patterns in metal concentrations, with much higher concentrations in winter. Sites near the Pb-Zn mine tailing reservoir exhibited higher metal contamination levels than other sites. A strong correlation between the enrichment factor and the levels of nonresidual fraction suggested that anthropogenic inputs were the main source of these metals. Mining industries (Cd, Zn, and Pb), natural sources (As, Ni, and Cu), and agricultural activities (Cr) were the primary sources of heavy metal pollution in biofilms, accounting for 44.43%, 33.32%, and 22.26% of the total metal accumulation, respectively. Moreover, the carcinogenic and noncarcinogenic risks via dermal contact of the studied elements in biofilms were typically acceptable. Notably, as concentration was the main factor influencing these risks in children and adults. This study provides evidence that natural epilithic periphyton may be a potential metal biomonitor in aquatic systems and provide supporting information for effective source regulation.

Effect of Drying-Rewetting cycles on the metal adsorption and tolerance of natural biofilms.

Drying-rewetting (D-RW) cycles can induce changes in biofilms by forcing the microbial community to tolerate and adapt to environmental pressure. Existing studies have mostly focused on the impact of D-RW cycles on the microbial community structure, and little attention has been paid to how D-RW cycles may change the biofilm tolerance and adsorption of heavy metals. We experimentally evaluated the effect of repeated D-RW cycles on the Cd2+ and Pb2+ adsorption and tolerance of biofilms. The equilibrium adsorption capacity of the biofilm decreased as the number of D-RW cycles was increased, which was attributed to a change in affinity between the biofilm and metal ions. For a binary metal system, the D-RW cycles affected the competitive adsorption of Cd2+ and Pb2+ by the biofilm. A synergistic effect was observed with one and three D-RW cycles, while an antagonistic effect was observed for the control film and five D-RW cycles. The tolerance of the biofilm to Cd2+ and Pb2+ increased with the number of D-RW cycles. The stress from the D-RW cycles may have increased the relative abundance of drought-tolerant bacteria, which altered the biofilm functions and thus indirectly affected the heavy metal adsorption capacity.

Enhanced Cd2+ adsorption and toxicity for microbial biofilms in the presence of TiO2 nanoparticles.

Titanium dioxide nanoparticles (TiO2 NPs) easily combine with other pollutants such as heavy metals because of their excellent physiochemical properties. However, how such an interaction may affect the binding behavior of metals onto biofilms remains largely unclear. This study, examined the effects of TiO2 NPs on Cd2+ accumulation and toxicity for natural periphytic biofilms were examined. The adsorption kinetics showed that adding 0.1 and 1 mg/L TiO2-NPs increased the Cd2+ adsorption of biofilms at equilibrium by 23.5% and 35.8%, respectively. However, adding 10 mg/L TiO2 NPs increased the Cd2+ adsorption of biofilms at equilibrium by only 1.9%. The adsorption isotherms indicate that the presence of TiO2 NPs considerably increased the Cd2+ adsorption capacity of the biofilms; however, this effect became less prominent at high TiO2 NP concentrations. The optimum pH for Cd2+ adsorption increased with increasing Cd2+ and TiO2 NP contents. At low concentrations, the coexistence of Cd2+ and TiO2 NPs may facilitate their respective accumulation by stimulating the secretion of extracellular polymeric substances and enhancing the microbial activity of the biofilm. The presence of TiO2 NPs increases the surface binding energy between Cd2+ and functional groups such as carboxyl groups, enhancing the Cd2+ accumulation on the biofilm.

Source apportionment and risk assessment of metal pollution in natural biofilms and surface water along the Lancang River, China.

Herein, surface water and periphytic biofilm samples were collected from 16 sites along the Lancang River, China, to assess the spatial distribution, enrichment factor (EF), potential ecological risk index (RI), and associated source-oriented health risks of heavy metal elements (As, Cd, Co, Cr, Cu, Ni, Pb, V, and Zn) in the samples. Results showed that the levels of heavy metals were significantly lower in the surface water samples than in the biofilm samples (one-way analysis of variance, p < 0.001). Moreover, 37.50 % of the biofilm samples were significantly polluted by these heavy metals with a mean EF of >5. As and V were the highest polluting metals, and the enrichment of Co and Ni were attributed to natural sources. RI assessment results showed a consistent ecological risk of As. Based on principal component analysis with multiple linear regression (PCA-MLR) and positive matrix factorization (PMF) models, the presence of heavy metal ions in the biofilm samples was largely attributed to industrial activities (PCA-MLR: 68.89 %; PMF: 76.39 %), followed by a mixed source of natural and agricultural activities (PCA-MLR: 18.12 %; PMF: 13.56 %), and traffic emissions (PCA-MLR: 12.99 %; PMF: 10.05 %). Both carcinogenic and noncarcinogenic risks for adults were negligible even though adults tended to be exposed to greater risk through ingestion. Source-specific risk evaluations indicated that industrial pollution was the most important source of health risks. Our findings highlight the potential threat of biofilms to the ecological and human health.

Drying and rewetting induce changes in biofilm characteristics and the subsequent release of metal ions.

Drying and rewetting can markedly influence the microbial structure and function of river biofilm communities and potentially result in the release of metal ions from biofilms containing metals. However, little information is available on the response of metal-enriched biofilms to drying and rewetting over time. In this study, natural biofilms were allowed to develop in four rotating annular bioreactors for 2-11 weeks, followed by drying for 5 days and rewetting for another 5 days. Subsequently, we assessed Zn, Cd, and As desorption from the biofilms and other related parameters (microbial community structure, biofilm morphology, enzyme activity, and surface components as well as characteristics). High-throughput sequencing of the 16 S rRNA gene and confocal laser scanning microscopy revealed that the biofilm architecture and bacterial communities were distinct in different growth phases and under drying and rewetting conditions (permutational multivariate analysis of variance; p = 0.001). Proteobacteria was the dominant bacterial phylum, accounting for 69.7-90.1% of the total content. Kinetic experiments revealed that the drying and rewetting process increased metal desorption from the biofilm matrix. The desorption of heavy metals was affected by the age of the biofilm, with the maximum amount of metal ions released from 2-week-old biofilms (one-way ANOVA, Zn: p < 0.001; Cd: p = 0.008; As: p < 0.001). The modifications in biofilm properties and decreased diversity of the bacterial community (paired t-test, p < 0.05) after drying and rewetting decreased the number of specific binding sites for metal ions. In addition, negatively charged arsenate and other anions in the liquid phase could compete with As ions for adsorption sites to promote the release of As(V) and/or reductive desorption of As(III). The results of this study and their interpretation are expected to help refine the behaviors of heavy metals in the aquatic environment.