The occurrence and development mechanisms of esophageal stricture: state of the art review.

BACKGROUND: Esophageal strictures significantly impair patient quality of life and present a therapeutic challenge, particularly due to the high recurrence post-ESD/EMR. Current treatments manage symptoms rather than addressing the disease's etiology. This review concentrates on the mechanisms of esophageal stricture formation and recurrence, seeking to highlight areas for potential therapeutic intervention. METHODS: A literature search was conducted through PUBMED using search terms: esophageal stricture, mucosal resection, submucosal dissection. Relevant articles were identified through manual review with reference lists reviewed for additional articles. RESULTS: Preclinical studies and data from animal studies suggest that the mechanisms that may lead to esophageal stricture include overdifferentiation of fibroblasts, inflammatory response that is not healed in time, impaired epithelial barrier function, and multimethod factors leading to it. Dysfunction of the epithelial barrier may be the initiating mechanism for esophageal stricture. Achieving perfect in-epithelialization by tissue-engineered fabrication of cell patches has been shown to be effective in the treatment and prevention of esophageal strictures. CONCLUSION: The development of esophageal stricture involves three stages: structural damage to the esophageal epithelial barrier (EEB), chronic inflammation, and severe fibrosis, in which dysfunction or damage to the EEB is the initiating mechanism leading to esophageal stricture. Re-epithelialization is essential for the treatment and prevention of esophageal stricture. This information will help clinicians or scientists to develop effective techniques to treat esophageal stricture in the future.

An unbiased approach of molecular characterization of the endometrium: toward defining endometrial-based infertility.

Infertility is a complex condition affecting millions of couples worldwide. The current definition of infertility, based on clinical criteria, fails to account for the molecular and cellular changes that may occur during the development of infertility. Recent advancements in sequencing technology and single-cell analysis offer new opportunities to gain a deeper understanding of these changes. The endometrium has a potential role in infertility and has been extensively studied to identify gene expression profiles associated with (impaired) endometrial receptivity. However, limited overlap among studies hampers the identification of relevant downstream pathways that could play a role in the development of endometrial-related infertility. To address these challenges, we propose sequencing the endometrial transcriptome of healthy and infertile women at the single-cell level to consistently identify molecular signatures. Establishing consensus on physiological patterns in endometrial samples can aid in identifying deviations in infertile patients. A similar strategy has been used with great success in cancer research. However, large collaborative initiatives, international uniform protocols of sample collection and processing are crucial to ensure reliability and reproducibility. Overall, the proposed approach holds promise for an objective and accurate classification of endometrial-based infertility and has the potential to improve diagnosis and treatment outcomes.

Analysis of CCND3 mutations in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL), accounts for 30-40% of newly diagnosed lymphomas, has an overall cure rate of approximately 60%. Despite previous reports suggesting a negative prognostic association between CCND3 mutations and Burkitt lymphoma, their prognostic implications in DLBCL remain controversial. To investigate this, we evaluated CCND3 mutation status in 2059 DLBCL patient samples from four database (integrated cohort) and additional 167 DLBCL patient samples in our center (JSPH cohort). The mutation was identified in 5.5% (113/2059) of the cases in the integrated cohort, with 86% (97/113) found in exon 5. Furthermore, P284, R271, I290 and Q276 are described as CCND3 mutation hotspots. CCND3 mutation was associated with decreased overall survival (OS) in the integrated cohort (P = 0.0407). Further subgroup analysis revealed that patients diagnosed as EZB subtype DLBCL by LymphGen algorithm with CCND3 mutations had poorer OS than patients diagnosed as EZB subtype without CCND3 mutations (P = 0.0140). Using the next-generation sequencing (NGS) in the JSPH cohort, it was found that both cell cycle and DNA replication pathways were highly upregulated in patients with CCND3 mutations. Our results suggest that CCND3 mutations can serve as a novel prognostic factor in DLBCL pathogenesis. Consequently, the development of personalized therapeutic strategies for DLBCL patients with CCND3 mutations might enhance their prognosis.

Identify truly high-risk TP53-mutated diffuse large B cell lymphoma patients and explore the underlying biological mechanisms.

TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.

Physiological Response to the COVID-19 Vaccine: Insights From a Prospective, Randomized, Single-Blinded, Crossover Trial.

BACKGROUND: Rapid development and implementation of vaccines constituted a crucial step in containing the COVID-19 pandemic. A comprehensive understanding of physiological responses to these vaccines is important to build trust in medicine. OBJECTIVE: This study aims to investigate temporal dynamics before and after COVID-19 vaccination in 4 physiological parameters as well as the duration of menstrual cycle phases. METHODS: In a prospective trial, 17,825 adults in the Netherlands wore a medical device on their wrist for up to 9 months. The device recorded their physiological signals and synchronized with a complementary smartphone app. By means of multilevel quadratic regression, we examined changes in wearable-recorded breathing rate, wrist skin temperature, heart rate, heart rate variability, and objectively assessed the duration of menstrual cycle phases in menstruating participants to assess the effects of COVID-19 vaccination. RESULTS: The recorded physiological signals demonstrated short-term increases in breathing rate and heart rate after COVID-19 vaccination followed by a prompt rebound to baseline levels likely reflecting biological mechanisms accompanying the immune response to vaccination. No sex differences were evident in the measured physiological responses. In menstruating participants, we found a 0.8% decrease in the duration of the menstrual phase following vaccination. CONCLUSIONS: The observed short-term changes suggest that COVID-19 vaccines are not associated with long-term biophysical issues. Taken together, our work provides valuable insights into continuous fluctuations of physiological responses to vaccination and highlights the importance of digital solutions in health care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-021-05241-5.

Dietary astaxanthin: an excellent carotenoid with multiple health benefits.

Astaxanthin is a carotenoid widely found in marine organisms and microorganisms. With extensive use in nutraceuticals, cosmetics, and animal feed, astaxanthin will have the largest share in the global market for carotenoids in the near future. Owing to its unique molecular features, astaxanthin has excellent antioxidant activity and holds promise for use in biochemical studies. This review focuses on the observed health benefits of dietary astaxanthin, as well as its underlying bioactivity mechanisms. Recent studies have increased our understanding of the role of isomerization and esterification in the structure-function relationship of dietary astaxanthin. Gut microbiota may involve the fate of astaxanthin during digestion and absorption; thus, further knowledge is needed to establish accurate recommendations for dietary intake of both healthy and special populations. Associated with the regulation of redox balance and multiple biological mechanisms, astaxanthin is proposed to affect oxidative stress, inflammation, cell death, and lipid metabolism in humans, thus exerting benefits for skin condition, eye health, cardiovascular system, neurological function, exercise performance, and immune response. Additionally, preclinical trials predict its potential effects such as intestinal flora regulation and anti-diabetic activity. Therefore, astaxanthin is worthy of further investigation for boosting human health, and wide applications in the food industry.

Water-lifting and aeration system improves water quality of drinking water reservoirs: Biological mechanism and field application.

Reservoirs have been served as the major source of drinking water for dozens of years. The water quality safety of large and medium reservoirs increasingly becomes the focus of public concern. Field test has proved that water-lifting and aeration system (WLAS) is a piece of effective equipment for in situ control and improvement of water quality. However, its intrinsic bioremediation mechanism, especially for nitrogen removal, still lacks in-depth investigation. Hence, the dynamic changes in water quality parameters, carbon source metabolism, species compositions and co-occurrence patterns of microbial communities were systematically studied in Jinpen Reservoir within a whole WLAS running cycle. The WLAS operation could efficiently reduce organic carbon (19.77%), nitrogen (21.55%) and phosphorus (65.60%), respectively. Biolog analysis revealed that the microbial metabolic capacities were enhanced via WLAS operation, especially in bottom water. High-throughput sequencing demonstrated that WLAS operation altered the diversity and distributions of microbial communities in the source water. The most dominant genus accountable for aerobic denitrification was identified as Dechloromonas. Furthermore, network analysis revealed that microorganisms interacted more closely through WLAS operation. Oxidation-reduction potential (ORP) and total nitrogen (TN) were regarded as the two main physicochemical parameters influencing microbial community structures, as confirmed by redundancy analysis (RDA) and Mantel test. Overall, the results will provide a scientific basis and an effective way for strengthening the in-situ bioremediation of micro-polluted source water.

Added Value of Biophysics to Study Lipid-Driven Biological Processes: The Case of Surfactins, a Class of Natural Amphiphile Molecules.

The role of membrane lipids is increasingly claimed to explain biological activities of natural amphiphile molecules. To decipher this role, biophysical studies with biomimetic membrane models are often helpful to obtain insights at the molecular and atomic levels. In this review, the added value of biophysics to study lipid-driven biological processes is illustrated using the case of surfactins, a class of natural lipopeptides produced by Bacillus sp. showing a broad range of biological activities. The mechanism of interaction of surfactins with biomimetic models showed to be dependent on the surfactins-to-lipid ratio with action as membrane disturber without membrane lysis at low and intermediate ratios and a membrane permeabilizing effect at higher ratios. These two mechanisms are relevant to explain surfactins' biological activities occurring without membrane lysis, such as their antiviral and plant immunity-eliciting activities, and the one involving cell lysis, such as their antibacterial and hemolytic activities. In both biological and biophysical studies, influence of surfactin structure and membrane lipids on the mechanisms was observed with a similar trend. Hence, biomimetic models represent interesting tools to elucidate the biological mechanisms targeting membrane lipids and can contribute to the development of new molecules for pharmaceutical or agronomic applications.

Metabolic and Transcriptomic Profiling Reveals Etiolated Mechanism in Huangyu Tea (Camellia sinensis) Leaves.

Leaf color is one of the key factors involved in determining the processing suitability of tea. It relates to differential accumulation of flavor compounds due to the different metabolic mechanisms. In recent years, photosensitive etiolation or albefaction is an interesting direction in tea research field. However, the molecular mechanism of color formation remains unclear since albino or etiolated mutants have different genetic backgrounds. In this study, wide-target metabolomic and transcriptomic analyses were used to reveal the biological mechanism of leaf etiolation for 'Huangyu', a bud mutant of 'Yinghong 9'. The results indicated that the reduction in the content of chlorophyll and the ratio of chlorophyll to carotenoids might be the biochemical reasons for the etiolation of 'Huangyu' tea leaves, while the content of zeaxanthin was significantly higher. The differentially expressed genes (DEGs) involved in chlorophyll and chloroplast biogenesis were the biomolecular reasons for the formation of green or yellow color in tea leaves. In addition, our results also revealed that the changes of DEGs involved in light-induced proteins and circadian rhythm promoted the adaptation of etiolated tea leaves to light stress. Variant colors of tea leaves indicated different directions in metabolic flux and accumulation of flavor compounds.

Efficacy of local anaesthetic and steroid combination in prevention of post-herpetic neuralgia: A meta-analysis.

Objective: The objective was to provide synthesized evidence on the efficacy of local anaesthetics and steroid injections for prevention and management of PHN, compared to the standard treatment using anti-viral and analgesic medications. The primary outcomes of interest were incidence of PHN and duration of neuralgic pain. Methods: Comprehensive searches were done systematically through PubMed, Scopus, Cochrane Central Register of Controlled Trials and Google scholar databases. Randomized controlled trials that compared the efficacy of local anaesthetics and steroid injections for preventing and managing PHN were included for this meta-analysis. A comprehensive search was done for papers published until 15th July 2021. Results: A total of 10 RCTs were included in the meta-analysis. In the overall pooled analyses, compared to standard care/placebo, those receiving a combination of local anaesthetic and steroid injection had 55% lower risk of PHN at 3 months from onset of rash (RR 0.45; 95% CI, 0.29; 0.70). Out of the different modes of intervention delivery i.e., intravenous, subcutaneous and nerve block, maximum beneficial effect in reducing the incidence of PHN was noted in nerve block (RR 0.55; 95% CI, 0.34, 0.89). Conclusions: The meta-analysis provides some evidence to support the use of combined local anaesthetic and steroids in reducing risk of post-herpetic neuralgia and duration of neuralgic pain in patients with herpes zoster rash.

Role of air pollution in systemic lupus erythematosus. / 空气污染在系统性红斑狼疮发生发展中的作用.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that can affect almost every organ in the human body. The etiology and pathogenesis are unclear. Recent studies have shown that pathogenesis and development of SLE result from the interaction between various internal and external factors. Current studies suggest that air pollution may increase the risk of SLE through multiple mechanisms such as inducing immune disorders, causing epigenetic changes, and inducing oxidative stress. Air pollution has a certain relationship with pulmonary interstitial lesions, lupus nephritis, decreased reproductive function and other system damages in SLE patients, and it is related to the occurrence and clinical outcomes of SLE. Air pollution has a potential role in the occurrence and development of SLE, providing a brand-new view on the early prevention and control of SLE.

Periodontology and pregnancy: An overview of biomedical and epidemiological evidence.

Women are particularly susceptible to developing gingival problems during pregnancy. In addition, periodontal disease in pregnant women may lead to adverse outcomes for both mother and infant, which have serious clinical and public health implications. Both scenarios have been extensively researched, helping to bring attention to pregnant women as an important and vulnerable population as it concerns periodontal health. The increase in gingival inflammation caused by hormonal changes in pregnant women is undisputed and has been studied and documented since the 1960s, although the exact etiology is not fully understood. The relationship between periodontal disease during pregnancy and adverse pregnancy outcomes is less substantiated, because of conflicting evidence. This review of the biomedical and epidemiologic literature provides an overview of both sides of this relationship and examines the potential mechanisms for developing periodontal disease during pregnancy and the proposed mechanisms by which periodontal disease leads to adverse pregnancy outcomes.

Discovery of 3,5-dimethylisoxazole derivatives as novel, potent inhibitors for bromodomain and extraterminal domain (BET) family.

Bromodomain and extra-terminal (BET) is a promising therapeutic target for various hematologic cancers. We used the BRD4 inhibitor compound 13 as a lead compound to develop a variety of compounds, and we introduced diverse groups into the position of the compound 13 orienting toward the ZA channel. A series of compounds (14-23, 38-41, 43, 47-49) bearing triazolopyridazine motif exhibited remarkable BRD4 protein inhibitory activities. Among them, compound 39 inhibited BRD4(BD1) protein with an IC50 of 0.003 µM was superior to lead compound 13. Meanwhile, compound 39 possess activity, IC50 = 2.1 µM, in antiproliferation activity against U266 cancer cells. On the other hand, compound 39 could arrest tumor cells into the G0/G1 phase and induce apoptosis, which was consistent with its results in inhibiting cell proliferation. Biological and biochemical data suggest that BRD4 protein might be a therapeutic target and that compound 39 is an excellent lead compound for further development.

Insights into complete nitrate removal in one-stage nitritation-anammox by coupling heterotrophic denitrification.

Nitritation-anammox has been considered to be the most promising process for nitrogen (N) removal from wastewater. However, the anammox reaction still produces an amount of nitrate, which cannot be removed further. This study hypothesizes that heterotrophic denitrification can be an appealing option to remove the residual nitrate in the one-stage nitritation-anammox process. Through monitoring N-removal performance and microbial community succession of a laboratory microaerobic reactor, the effect of four different levels of oxygen supply on nitrate removal was investigated. The reactor was continuously fed with real manure-free piggery wastewater containing ~240 mg NH4+-N/L and chemical oxygen demand (COD)/total nitrogen (TN) ratio of less than 1 for 180 days. With a high influent loading rate of 0.7 kg N/(m3·d), efficient total nitrogen removal (>80 %) was achieved during stable operation of dissolved oxygen (DO) concentrations between 0.3 and 0.6 mg O2/L, indicating N-removal via the nitritation-anammox pathway in the low-carbon wastewater treatment. At the same time, the effluent nitrate reduced with decreased oxygen supply and completely depleted at DO of 0.3 ± 0.1 mg O2/L. In addition to oxygen, preventing ammonia nitrogen from falling to very low levels (<10 mg/L) could be also useful for the complete nitrate removal and stable nitritation-anammox. 16S rRNA gene-based analyses confirmed a complex microbial community including nitrifiers, denitrifiers and anammox bacteria in the biomass of the reactor. Collectively, this study provides new insights into high-level N-removal of a nitritation-anammox process by complete nitrate depletion.

Application of animal experimental models in the research of schizophrenia.

Schizophrenia is a relatively common but serious mental illness that results in a heavy burden to patients, their families, and society. The disease can be triggered by multiple factors, while the specific pathogenesis remains unclear. The development of effective therapeutic drugs for schizophrenia relies on a comprehensive understanding of the basic biology and pathophysiology of the disease. Therefore, effective animal experimental models play a vital role in the study of schizophrenia. Based on different molecular mechanisms and modeling methods, the currently used experimental animal experimental models of schizophrenia can be divided into four categories that can better simulate the clinical symptoms and the interplay between susceptible genes and the environment: neurodevelopmental, drug-induced, genetic-engineering, and genetic-environmental interaction of animal experimental models. Each of these categories contains multiple subtypes, which has its own advantages and disadvantages and therefore requires careful selection in a research application. The emergence and utilization of these models are promising in the prediction of the risk of schizophrenia at the molecular level, which will shed light on effective and targeted treatment at the genetic level.

Diabetes as a risk factor for periodontal disease-plausible mechanisms.

The present narrative review examines the scientific evidence of the biological mechanisms that may link periodontitis and diabetes, as a source of comorbidity. Publications regarding periodontitis and diabetes, in human, animals, and in vitro were screened for their relevance. Periodontal microbiome studies indicate a possible association between altered glucose metabolism in prediabetes and diabetes and changes in the periodontal microbiome. Coinciding with this, hyperglycemia enhances expression of pathogen receptors, which enhance host response to the dysbiotic microbiome. Hyperglycemia also promotes pro-inflammatory response independently or via the advanced glycation end product/receptor for advanced glycation end product pathway. These processes excite cellular tissue destruction functions, which further enhance pro-inflammatory cytokines expression and alteration in the RANKL/osteoprotegerin ratio, promoting formation and activation of osteoclasts. The evidence supports the role of several pathogenic mechanisms in the path of true causal comorbidity between poorly controlled diabetes and periodontitis. However, further research is needed to better understand these mechanisms and to explore other mechanisms.

The development and understanding of intracranial aneurysm based on rabbit model.

In modern society, intracranial aneurysms have seriously affected people's life. To better study and treat intracranial aneurysm, animal models are ideal candidates to perform biological research and preclinical endovascular device testing. Rabbit aneurysm model is one of the most commonly used animal models, and the rabbit aneurysms share similarities in histology, morphology, and hemodynamic aspects with human intracranial aneurysms, which is an ideal model for intracranial aneurysm pre-clinical and basic research. In this review, we will summarize the main methods of establishing rabbit aneurysms model and will further discuss the current biological mechanisms of intracranial aneurysms based on rabbit model. Further improvements of rabbit aneurysm model and more deep studies based on this model are needed to provide new insights into studying and clinical treating intracranial aneurysm.

Regulating appetite in broilers for improving body and muscle development - A review.

Appetite is the desire for feed and water and the voluntary intake of feed and is an important regulator of livestock productivity and animal health. Economic traits such as growth rate and muscle development (meat deposition) in broilers are directly correlated to appetite. Factors that may influence appetite include environmental factors, such as stress and temperature variation, and animal-specific factors, such as learning period, eating capacity and preferences. Feed preferences have been reported to be determined in early life, and this period is important in broilers due to their fast growth and relatively short growth trajectories. This may be of importance when contemplating the use of more circular and sustainable feeds and the optimization of appetite for these feeds. The objective of this review was to review the biological mechanisms underlying appetite using data from human, animal and bird models and to consider the option for modulating appetite particularly as it relates to broiler chickens.

Responses of serum chemokines to dramatic changes of air pollution levels, a panel study.

Background: Despite the in vitro and in vivo evidence, studies are limited in evaluating whether chemokines are potential inflammatory mediators in response to air pollution exposure in humans. Methods: We conducted a panel study coinciding with the Beijing Olympics, when temporary air pollution controls were implemented. We measured a suite of serum chemokines among healthy adults before, during and after the Olympics, respectively. Linear mixed-effect models were used to evaluate changes in chemokine levels over the three time periods. Results: In response to the 50% drop in air pollution levels during the games, levels of RANTES, MCP-2, and TARC decreased by 25.8%, 20.9% and 35.3%, respectively (p < 0.001) from pre-Olympics, and then increased by 45.8%, 34.9% and 61.5%, respectively (p < 0.001) after the games when air pollution levels went up again. Similar patterns were observed in subgroup analyses by sex, age, smoking and body mass index. GRO-α and IL-8 decreased significantly during the games (22.5% and 30.4%), and increased non-significantly after the games. Eotaxin-1 only increased significantly from during- to post-games. Conclusions: The strongest associations with air pollution levels were observed among RANTES, TARC and MCP-2. Those chemokines may play important roles in the air pollution-induced inflammatory pathway.

Mesenchymal Stem Cells of Dental Origin for Inducing Tissue Regeneration in Periodontitis: A Mini-Review.

Periodontitis is a chronic disease that begins with a period of inflammation of the supporting tissues of the teeth table and then progresses, destroying the tissues until loss of the teeth occurs. The restoration of the damaged dental support apparatus is an extremely complex process due to the regeneration of the cementum, the periodontal ligament, and the alveolar bone. Conventional treatment relies on synthetic materials that fill defects and replace lost dental tissue, but these approaches are not substitutes for a real regeneration of tissue. To address this, there are several approaches to tissue engineering for regenerative dentistry, among them, the use of stem cells. Mesenchymal stem cells (MSC) can be obtained from various sources of adult tissues, such as bone marrow, adipose tissue, skin, and tissues of the orofacial area. MSC of dental origin, such as those found in the bone marrow, have immunosuppressive and immunotolerant properties, multipotency, high proliferation rates, and the capacity for tissue repair. However, they are poorly used as sources of tissue for therapeutic purposes. Their accessibility makes them an attractive source of mesenchymal stem cells, so this review describes the field of dental stem cell research and proposes a potential mechanism involved in periodontal tissue regeneration induced by dental MSC.