Single-cell sequencing reveals lung cell fate evolution initiated by smoking to explore gene predictions of correlative diseases.

Continuous smoking leads to adaptive regulation and physiological changes in lung tissue and cells, and is an inductive factor for many diseases, making smokers face the risk of malignant and nonmalignant diseases. The impact of research in this area is getting more and more in-depth, but the stimulant effect, mechanism of action and response mechanism of the main cells in the lungs caused by smoke components have not yet been fully elucidated, and the early diagnosis and identification of various diseases induced by smoke toxins have not yet formed a systematic relationship method. In this study, single-cell transcriptome data were generated from three lung samples of smokers and nonsmokers through scRNA-seq technology, revealing the influence of smoking on lung tissue and cells and the changes in immune response. The results show that: through UMAP cell clustering, 16 intermediate cell states of 23 cell clusters of the four main cell types in the lung are revealed, the differences of the main cell groups between smokers and nonsmokers are explained, and the human lung cells are clarified. Components and their marker genes, screen for new marker genes that can be used in the evolution of intermediate-state cells, and at the same time, the analysis of lung cell subgroups reveals the changes in the intermediate state of cells under smoke stimulation, forming a subtype intermediate state cell map. Pseudo-time ordering analysis, to determine the pattern of dynamic processes experienced by cells, differential expression analysis of different branch cells, to clarify the expression rules of cells at different positions, to clarify the evolution process of the intermediate state of cells, and to clarify the response of lung tissue and cells to smoke components mechanism. The development of this study provides new diagnosis and treatment ideas for early disease detection, identification, disease prevention and treatment of patients with smoking-related diseases, and lays a theoretical foundation based on cell and molecular regulation.

Integrating bioinformatic resources to identify characteristics of rheumatoid arthritis-related usual interstitial pneumonia.

BACKGROUND: Rheumatoid arthritis (RA) is often accompanied by a common extra-articular manifestation known as RA-related usual interstitial pneumonia (RA-UIP), which is associated with a poor prognosis. However, the mechanism remains unclear. To identify potential mechanisms, we conducted bioinformatics analysis based on high-throughput sequencing of the Gene Expression Omnibus (GEO) database. RESULTS: Weighted gene co-expression network analysis (WGCNA) analysis identified 2 RA-positive related modules and 4 idiopathic pulmonary fibrosis (IPF)-positive related modules. A total of 553 overlapped differentially expressed genes (DEG) were obtained, of which 144 in the above modules were further analyzed. The biological process of "oxidative phosphorylation" was found to be the most relevant with both RA and IPF. Additionally, 498 up-regulated genes in lung tissues of RA-UIP were screened out and enriched by 7 clusters, of which 3 were closely related to immune regulation. The analysis of immune infiltration showed a characteristic distribution of peripheral immune cells in RA-UIP, compared with IPF-UIP in lung tissues. CONCLUSIONS: These results describe the complex molecular and functional landscape of RA-UIP, which will help illustrate the molecular pathological mechanism of RA-UIP and identify new biomarkers and therapeutic targets for RA-UIP in the future.

A Study on Autophagy Related Biomarkers in Alzheimer's Disease Based on Bioinformatics.

Alzheimer's disease (AD) is a neurodegenerative disease with an annual incidence increase that poses significant health risks to people. However, the pathogenesis of AD is still unclear. Autophagy, as an intracellular mechanism can degrade damaged cellular components and abnormal proteins, which is closely related to AD pathology. The goal of this work is to uncover the intimate association between autophagy and AD, and to mine potential autophagy-related AD biomarkers by identifying key differentially expressed autophagy genes (DEAGs) and exploring the potential functions of these genes. GSE63061 and GSE140831 gene expression profiles of AD were downloaded from the Gene Expression Omnibus (GEO) database. R language was used to standardize and differentially expressed genes (DEGs) of AD expression profiles. A total of 259 autophagy-related genes were discovered through the autophagy gene databases ATD and HADb. The differential genes of AD and autophagy genes were integrated and analyzed to screen out DEAGs. Then the potential biological functions of DEAGs were predicted, and Cytoscape software was used to detect the key DEAGs. There were ten DEAGs associated with the AD development, including nine up-regulated genes (CAPNS1, GAPDH, IKBKB, LAMP1, LAMP2, MAPK1, PRKCD, RAB24, RAF1) and one down-regulated gene (CASP1). The correlation analysis reveals the potential correlation among 10 core DEAGs. Finally, the significance of the detected DEAGs expression was verified, and the value of DEAGs in AD pathology was detected by the receiver operating characteristic curve. The area under the curve values indicated that ten DEAGs are potentially valuable for the study of the pathological mechanism and may become biomarkers of AD. This pathway analysis and DEAG screening in this study found a strong association between autophagy-related genes and AD, providing new insights into the pathological progression of AD. Exploring the relationship between autophagy and AD: analysis of genes associated with autophagy in pathological mechanisms of AD using bioinformatics. 10 autophagy-related genes play an important role in the pathological mechanisms of AD.

Identification of lncRNA-miRNA-mRNA Regulatory Network and Therapeutic Agents for Skin Aging by Bioinformatics Analysis.

Skin aging is the most intuitive manifestation of aging. Skin aging inevitably leads to cosmetic and psychological problems, and even diseases. The present study aims to research the pathological and molecular mechanisms underlying skin aging and identify the therapeutic agents for reversing skin aging. Two available gene expression datasets (GSE55118 and GSE72264) for skin aging were downloaded from Gene Expression Omnibus, followed by bioinformatic analyses performed on the datasets. Firstly, 169 crucial mRNAs, 27 crucial miRNAs and 50 crucial lncRNAs closely related to skin aging were identified by weighted gene co-expression network analysis. Then, function Enrichment Analysis performed by Metascape database showed that skin aging involves a variety of biological functions, such as detection of stimulus, response to steroid hormone and water channel activity, regulation of muscle contraction. Next, ten hub genes including AQP4, TRPM8, TBR1, NTSR2, MPPED1, BARHL2, PAX9, CPN1, CES3, and CHGB were screened out by the protein-protein interaction analysis. Next, the "lncRNA-miRNA-mRNA" network and the "lncRNA-miRNA-hub mRNA" network were constructed to explore the competing endogenous RNAs mechanism of skin aging. Finally, ten significant potential small molecules mitigating skin aging were screened using CMAP platform, including tretinoin, pifithrin, selamectin, entinostat, bretazenil, syringic-acid, BRD-K96475865, emedastine, abacavir, and rotenone, and their reliability was verified by molecular docking experiments. The present study provided basis for revealing the molecular mechanism of skin aging and identified the potential candidate drugs for mitigating skin aging.

Preclinical study of diabetic foot ulcers: From pathogenesis to vivo/vitro models and clinical therapeutic transformation.

Diabetic foot ulcer (DFU), a common intractable chronic complication of diabetes mellitus (DM), has a prevalence of up to 25%, with more than 17% of the affected patients at risk of amputation or even death. Vascular risk factors, including vascular stenosis or occlusion, dyslipidemia, impaired neurosensory and motor function, and skin infection caused by trauma, all increase the risk of DFU in patients with diabetes. Therefore, diabetic foot is not a single pathogenesis. Preclinical studies have contributed greatly to the pathogenesis determination and efficacy evaluation of DFU. Many therapeutic tools are currently being investigated using DFU animal models for effective clinical translation. However, preclinical animal models that completely mimic the pathogenesis of DFU remain unexplored. Therefore, in this review, the preparation methods and evaluation criteria of DFU animal models with three major pathological mechanisms: neuropathy, angiopathy and DFU infection were discussed in detail. And the advantages and disadvantages of various DFU animal models for clinical sign simulation. Furthermore, the current status of vitro models of DFU and some preclinical studies have been transformed into clinical treatment programs, such as medical dressings, growth factor therapy, 3D bioprinting and pre-vascularization, Traditional Chinese Medicine treatment. However, because of the complexity of the pathological mechanism of DFU, the clinical transformation of DFU model still faces many challenges. We need to further optimize the existing preclinical studies of DFU to provide an effective animal platform for the future study of pathophysiology and clinical treatment of DFU.

Atopic March or Atopic Multimorbidity-Overview of Current Research.

The atopic march encompasses a sequence of allergic conditions, including atopic dermatitis, food allergy, allergic rhinitis, and asthma, that frequently develop in a sequential pattern within the same individual. It was introduced as a conceptual framework aimed at elucidating the developmental trajectory of allergic conditions during childhood. Following the introduction of this concept, it was initially believed that the atopic march represented the sole and definitive trajectory of the development of allergic diseases. However, this perspective evolved with the emergence of new longitudinal studies, which revealed that the evolution of allergic diseases is far more intricate. It involves numerous immunological pathological mechanisms and may not align entirely with the traditional concept of the atopic march. The objective of our review is to portray the atopic march alongside other patterns in the development of childhood allergic diseases, with a specific emphasis on the potential for a personalized approach to the prevention, diagnosis, and treatment of atopic conditions.

Between early and established chronic pancreatitis: A proposal of "acinar-ductal hybrid mechanism".

BACKGROUND/OBJECTIVES: The recently proposed "new mechanistic definition of chronic pancreatitis (CP)" categorized early CP as a reversible condition. However, there is no clear explanation regarding the pathological condition of early CP, the reason for the development of the disease in only a small portion of the patients with risk factors, and the mechanism for transition from a reversible pathological condition to an irreversible one. METHODS: Based on the available information, a mechanism that could provide answers to the queries associated with CP was proposed. RESULTS: Acinar-ductal coordination is very important for the physiological secretion of pancreatic juice. Inflammation originating from acinar cells undermines the function of proximal ducts and leads to a vicious cycle of sustained inflammation by increasing the viscosity and decreasing the alkalinity of pancreatic juice. Persistent elevation of ductal pressure due to stagnation of pancreatic juice caused by protein plugs, stones, or fibrous scar of ducts converts the reversible pathological condition of early CP to an irreversible one. Diagnostic criteria for early CP proposed by Japanese researchers have enabled to the recognition of patients showing a progression from early to established CP. However, most patients diagnosed with early CP do not experience progression of the disease, suggesting the inadequate specificity of the criteria. CONCLUSION: The "acinar-ductal hybrid mechanism" may explain the pathological condition and progression of early CP. To diagnose early CP more accurately, it is essential to discover specific biomarkers that can discriminate "early CP" from "acute pancreatitis (AP)/recurrent acute pancreatitis (RAP)" and "established CP." Therapeutic intervention in clinical practices through various new approaches is expected to improve the prognosis of patients with CP.

Hypertensive heart disease and myocardial fibrosis: How traditional Chinese medicine can help addressing unmet therapeutical needs.

Long-term elevated blood pressure will increase the cardiac load and lead to myocardial fibrosis (MF). A variety of pathological mechanisms and signal transduction pathways are involved in the process of hypertensive MF, which is of great significance for the occurrence and development of ventricular dilatation and heart failure. MF is the pathological basis of hypertensive heart disease (HHD), and blood pressure control is the key to delaying MF and reducing the occurrence of cardiovascular events. Although a large number of experimental results suggest that anti-MF drug therapy has made great progress, the conclusions of relevant clinical trials are still not optimistic, and it is urgent to find new effective anti-MF medicine. The clinical efficacy of traditional Chinese medicine (TCM) in the treatment of MF in HHD is obvious, and some achievements have been made in the mechanism research. Studies have confirmed that a variety of TCM compound prescription and natural compounds play different degrees of inhibitory effect on MF. In this study, we reviewed the pathogenesis of MF in HHD and the current drug treatment strategies, summarized the latest research progress of TCM in the treatment of MF in HHD, and demonstrated the mechanism of its cardiac protective effect. Finally, we pointed out the limitations of the current study and prospected the future research of TCM.

Lipoxin alleviates oxidative stress: a state-of-the-art review.

OBJECTIVE: This review aims to summarize the capability of lipoxin in regulating oxidative stress. BACKGROUND: Oxidative stress is defined as an imbalance between the production of free radicals and the antioxidant system, and it is associated with the existence of a large number of oxidation products, such as reactive oxygen species (ROS) and reaction nitrogen species (RNS), causing damage to human tissues through immunoinflammatory responses. Therefore, reducing oxidative stress is vital to alleviate pathological damage. Lipoxin, an acronym for lipoxygenase interaction product, is a bioactive autacoid metabolite of arachidonic acid made by various cell types. Previous studies have shown that lipoxin is associated with a variety of biological functions, including anti-inflammatory, regulating immune responses, promoting the repair of damaged cells, etc. The deficiency of lipoxin is a critical pathological mechanism in different diseases. Moreover, the ability of lipoxin to attenuate oxidative stress is noteworthy, thereby protecting the human body from diverse diseases. METHODS: We searched papers from PubMed database using search terms, such as lipoxin, lipoxin A4, oxidative stress, and other relevant terms. RESULTS: A total of 103 articles published over the past 20 years were identified for inclusion. We summarized the capability of lipoxin in regulating oxidative stress and mechanism. CONCLUSION: Lipoxin is provided with a protective role in attenuating oxidative stress.

Potential role of gut microbiota and its metabolites in radiation-induced intestinal damage.

Radiation-induced intestinal damage (RIID) is a serious disease with limited effective treatment. Nuclear explosion, nuclear release, nuclear application and especially radiation therapy are all highly likely to cause radioactive intestinal damage. The intestinal microecology is an organic whole with a symbiotic relationship formed by the interaction between a relatively stable microbial community living in the intestinal tract and the host. Imbalance and disorders of intestinal microecology are related to the occurrence and development of multiple systemic diseases, especially intestinal diseases. Increasing evidence indicates that the gut microbiota and its metabolites play an important role in the pathogenesis and prevention of RIID. Radiation leads to gut microbiota imbalance, including a decrease in the number of beneficial bacteria and an increase in the number of harmful bacteria that cause RIID. In this review, we describe the pathological mechanisms of RIID, the changes in intestinal microbiota, the metabolites induced by radiation, and their mechanism in RIID. Finally, the mechanisms of various methods for regulating the microbiota in the treatment of RIID are summarized.

[Mechanism of Impaired Cognitive Function in Patients with Chronic Kidney Disease].

Each stage of chronic kidney disease has a high risk of cognitive dysfunction.The decline of cognitive function will affect the daily life and treatment compliance of the patients with chronic kidney disease and increase the patients' risk of death and public health burden,which has aroused widespread concern.However,the specific mechanism of cognitive impairment in the patients with chronic kidney disease remains unclear.This paper summarizes the possible association mechanisms,related indicators,and impaired cognitive domains,aiming to provide a theoretical basis for the early diagnosis and slow down the progression of the cognitive impairment associated with chronic kidney disease.

WISP-2, an upregulated gene in hip cartilage from the DDH model rats, induces chondrocyte apoptosis through PPARγ in vitro.

Chondrocyte apoptosis plays an important role in the developmental dysplasia of the hip (DDH) development. It has been found that WNT1 inducible signaling pathway protein 2 (WISP-2) and peroxisome proliferator-activated receptor γ (PPARγ) are involved in cell apoptosis. In this study, we performed the straight-leg swaddling DDH rat model and we found that cartilage degradation and chondrocyte apoptosis were remarkably increased in DDH rats in vivo. Moreover, we found that WISP-2 was upregulated in hip acetabular cartilage of DDH rats compared to control rats. Next, the effects of WISP-2 on chondrocyte apoptosis and its possible underlying mechanism were examined in vitro. The lentivirus-mediated gain- and loss-of-function experiments of WISP-2 and peroxisome proliferator-activated receptor γ (PPARγ) for cell viability and apoptosis were performed in primary rat chondrocytes. The results showed that the overexpression of WISP-2 induced chondrocyte apoptosis, and knockdown of WISP-2 could suppress the chondrocyte apoptosis induced by advanced glycation end products (AGE). Additionally, WISP-2 could negatively regulate the expression of PPARγ in chondrocytes. Moreover, the knockdown of PPARγ promoted chondrocyte apoptosis and overexpression of PPARγ abated the increased apoptosis and decreased cell viability of chondrocytes induced by WISP-2. This study demonstrated that WISP-2 might contribute to chondrocyte apoptosis of hip acetabular cartilage through regulating PPARγ expression and activation, which may play an important role in the development of DDH.

Emodin-induced autophagic cell death hinders epithelial-mesenchymal transition via regulation of BMP-7/TGF-ß1 in renal fibrosis.

We aim to explore the effects of emodin and its mechanisms on renal fibrosis (RF). We firstly modeled adriamycin-induced rat RF with unilateral nephrectomy. In vivo and in vitro pharmacological experiments were performed in this study. The presence of collagen deposition was detected by Masson staining. To verify whether emodin attenuates RF by monitoring autophagy, the immunohistochemistry staining for autophagy protein LC3B was performed. We conducted western blot to detect the expression of the autophagy-related proteins in EMT in vitro model after treating with emotin and BMP-7. In vivo, we demonstrated that emodin could improve renal dysfunction and decrease pathological damage of the kidney by activation of autophagy and inhibition of EMT. Upregulation of BMP-7 was recorded in the RF rats subjected to emodin treatment. In vitro studies, emodin has the capacity of reversing EMT and activating autophagy, and emodin could regulate the expression of BMP-7. The results revealed that the attenuation of EMT by emodin could be blocked after the inhibition of BMP-7 and suppression of autophagy. Our findings demonstrated that emodin alleviates EMT during RF by actuating autophagy through BMP-7, suggesting a role of BMP-7 in RF treatment and prevention.

The toxicity of cell therapy: Mechanism, manifestations, and challenges.

Adoptive cell therapy (ACT), including tumor-infiltrating lymphocytes (TILs), T cell receptor engineered T cell (TCR-T), and chimeric antigen receptor engineered T cell (CAR-T), has shown significant clinical benefits for cancer treatment. However, all of these ACT therapies are associated with toxicities from mild to life threatening in clinic. Common ACT-related toxicities include cytokine release syndrome (CRS) resulting from immune activation, neurological toxicity, on-target/off tumor or off-target toxicities, and toxicities associated with lymphodepletion preconditioning and high does IL-2 administration. This review summarizes clinical manifestations of adverse events associated with ACT treatment and discusses the underlying pathological mechanisms. Moreover, challenges and opportunities of managing ACT-related toxicities have been discussed to give an indication of how to improve the safety of ACT treatment without dampening the therapeutic effect.

Physiological and pathological regulation of autophagy in pregnancy.

Autophagy exists widely in eukaryotic cells and is regulated by a variety of molecular mechanisms. Its physiological functions include providing energy, maintaining cell homeostasis, and promoting apoptosis of abnormal cells. At present, the regulation of autophagy in tumor, degenerative disease, and cardiovascular disease has attracted much attention. Gradually, the role of autophagy in pregnancy tends to be valued. The previous literature has shown that autophagy can influence the occurrence and maintenance of pregnancy from three aspects: embryo (affecting the process of fertilization and embryonic development and the function of trophoblast cells), maternal (decidualization), and maternal-to-fetal immune crosstalk. Undoubtedly, abnormalities in autophagy levels are associated with a variety of pregnancy complications, such as preeclampsia, fetal growth restriction, and preterm delivery which have been proven by human, animal, and in vitro experiments. The regulation of autophagy is expected to be a target for the treatment of these pregnancy complications. This article reviews the research on autophagy, especially about its physiological and pathological regulation during pregnancy.

Research perspective in the clinical management of Kawasaki disease.

This study examines research perspective in the clinical diagnosis, treatment, and prevention of cardiovascular complications in Kawasaki Disease (KD). Starting with an overview of the disease, it introduces KD's clinical manifestations, etiology, epidemiological features, and its impact on the cardiovascular system. Subsequently, the study discusses in detail the diagnostic methods, pathological mechanisms, and treatment strategies for KD, including foundational and emerging approaches such as high-dose intravenous immunoglobulin and aspirin therapy, biologic therapy, and corticosteroid pulse therapy. Additionally, it outlines strategies for preventing cardiovascular complications, including early risk assessment and long-term management. The study also explores the intersection of the COVID-19 pandemic with an increase in KD-like symptoms, emphasizing the need for further studies on the association between SARS-CoV-2 and KD. Lastly, it explores future research directions to enhance understanding of KD and improve patient outcomes and quality of life. This study provides valuable insights into the comprehensive treatment and management of KD and highlights avenues for future research.

Stem Cell-Based Approaches in Parkinson's Disease Research.

Parkinson's disease (PD) is a neurodegenerative condition characterized by the loss of midbrain dopaminergic neurons, leading to motor symptoms. While current treatments provide limited relief, they don't alter disease progression. Stem cell technology, involving patient-specific stem cell-derived neurons, offers a promising avenue for research and personalized regenerative therapies. This article reviews the potential of stem cell-based research in PD, summarizing ongoing efforts, their limitations, and introducing innovative research models. The integration of stem cell technology and advanced models promises to enhance our understanding and treatment strategies for PD.

The Impact of Microglia on Neurodevelopment and Brain Function in Autism.

Microglia, as one of the main types of glial cells in the central nervous system (CNS), are widely distributed throughout the brain and spinal cord. The normal number and function of microglia are very important for maintaining homeostasis in the CNS. In recent years, scientists have paid widespread attention to the role of microglia in the CNS. Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder, and patients with ASD have severe deficits in behavior, social skills, and communication. Most previous studies on ASD have focused on neuronal pathological changes, such as increased cell proliferation, accelerated neuronal differentiation, impaired synaptic development, and reduced neuronal spontaneous and synchronous activity. Currently, more and more research has found that microglia, as immune cells, can promote neurogenesis and synaptic pruning to maintain CNS homeostasis. They can usually reduce unnecessary synaptic connections early in life. Some researchers have proposed that many pathological phenotypes of ASD may be caused by microglial abnormalities. Based on this, we summarize recent research on microglia in ASD, focusing on the function of microglia and neurodevelopmental abnormalities. We aim to clarify the essential factors influenced by microglia in ASD and explore the possibility of microglia-related pathways as potential research targets for ASD.

Monoclonal antibody therapy for Alzheimer's disease focusing on intracerebral targets.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Due to the complexity of the disorder and the presence of the blood-brain barrier (BBB), its drug discovery and development are facing enormous challenges, especially after several failures of monoclonal antibody (mAb) trials. Nevertheless, the Food and Drug Administration's approval of the mAb aducanumab has ushered in a new day. As we better understand the disease's pathogenesis and identify novel intracerebral therapeutic targets, antibody-based therapies have advanced over the past few years. The mAb drugs targeting ß-amyloid or hyperphosphorylated tau protein are the focus of the current research. Massive neuronal loss and glial cell-mediated inflammation are also the vital pathological hallmarks of AD, signaling a new direction for research on mAb drugs. We have elucidated the mechanisms by which AD-specific mAbs cross the BBB to bind to targets. In order to investigate therapeutic approaches to treat AD, this review focuses on the promising mAbs targeting intracerebral dysfunction and related strategies to cross the BBB.

Glucose metabolism reprogramming in gynecologic malignant tumors.

The incidence and mortality of gynecological tumors are progressively increasing due to factors such as obesity, viral infection, unhealthy habits, as well as social and economic pressures. Consequently, it has emerged as a significant threat to women's health. Numerous studies have revealed the remarkable metabolic activity of tumor cells in glycolysis and its ability to influence malignant biological behavior through specific mechanisms. Therefore, it is crucial for patients and gynecologists to comprehend the role of glycolytic proteins, regulatory molecules, and signaling pathways in tumorigenesis, progression, and treatment. This article aims to review the correlation between abnormal glucose metabolism and gynecologic tumors including cervical cancer (CC), endometrial carcinoma (EC), and ovarian cancer (OC). The findings from this research will provide valuable scientific insights for early screening, timely diagnosis and treatment interventions while also aiding in the prevention of recurrence among individuals with gynecological tumors.