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Air pollution is a global issue that threatens human health. In recent years, more and more studies have found that air pollution is closely related to the occurrence of depression. As a serious neuropsychiatric disorder whose incidence is rising rapidly year by year, depression has become an invisible killer of public health. At present, studies on the correlation between air pollution and depression are still very limited, and the underlying molecular mechanisms by which air pollution affects depression are not clear. Based on existing epidemiological and toxicological studies, this paper provided a review of the relationship between air pollution and depression and the possible biological mechanisms, with a focus on the relationship between air pollution and depression indicators and the possible factors affecting depression such as types of air pollutants, exposure time, age and health status of study subjects. In addition, the potential roles of neuroinflammation, oxidative stress, neurogenesis, and apoptosis in the process of air pollution-induced depression were also discussed in order to provide a scientific basis for the prevention and treatment of air pollution-induced depression.
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Cholesterol metabolism is a hot topic in exploration of cancer treatment in recent years,and its complex mechanism of action potentially lays a molecular foundation related to lipid-cancer.However,most studies focus only on cholesterol as a product to understand and analyze the progress of cancer,ignoring the phased effects of related derivatives,regulatory proteins and immune cells in its metabolic process,so whether to find targets to regulate colorectal cancer(CRC)from the cholesterol metabolic pathway has become a research focus.This paper reviews the molecular mechanism and the role of signaling pathways in metabolic reprogramming of CRC starting from the abnormal intracellular cholesterol metabolic pathway in order to provide new ideas for the targeted cholesterol therapy of CRC.
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Narciclasine(NCS),a hymenocallis littoralis alkaloid extracted from the bulbs of the genus Narcissus in the Lycoriaceae family,has been proven to have significant anti-tumor activity against a variety of tumor cells.The antitumor mechanisms of NCS are diverse and NCS exhibits antitumor effects through different pathways,which adapts to the current trend of developing multi-target anti-tumor drugs.This review introduces the research progress of the anti-tumor activity and mechanism of NCS in recent years based on the inhibitory effect of NCS on gastric cancer cells,oral cancer cells,polymorphous glioblastoma cells,colon cancer cells,breast cancer cells,melanoma cells and primary exudative lymphoma cells,aiming to provide ideas and references for the research and development,and design of NCS type anti-tumor drugs in the future.
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Diabetic retinopathy（DR） and coronary heart disease（CHD） are both major chronic vascular complications that seriously jeopardize the health of the population and often occur together in clinical practice， it is of great clinical value to actively explore the association between the two in the process of disease development and methods of prevention and treatment of modern medicine and traditional Chinese medicine（TCM）. According to TCM， the heart and eyes physiologically communicate with each other by taking Qi， blood and veins as bridges， blood stasis obstructing collaterals is the common TCM etiology of DR and CHD， whose mechanism involves inflammation， oxidative stress and endothelial dysfunction. Promoting blood circulation and removing blood stasis plays an important role in the same treatment for different diseases and prevention and treatment of comorbidities， possibly by inhibiting the expression of interleukin-1β（IL-1β）， endothelin-1（ET-1） and hypoxia inducible factor-1α/vascular endothelial growth factor（HIF-1α/VEGF）， regulating phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin（PI3K/Akt/mTOR） pathway， initiating adenosine monophosphate（AMP）-activated protein kinase/silent information regulator 1（AMPK/SIRT1） and nuclear transcription factor erythroid 2-related factor 2/heme oxygenase-1（Nrf2/HO-1） signaling pathways， inhibiting Hippo/Yes-associated protein（Hippo/YAP） signaling pathway， inhibiting mitochondrial permeability transition pore and anti-platelet agglutination for treating DR and CHD， which provides a multi-component， multi-pathway and multi-target selection strategies and ideas for the prevention and treatment of DR and CHD by TCM from a biological perspective. Based on this， subsequent studies should focus on constructing clinically relevant comorbidity models， conducting multicenter prospective studies， and fully utilizing artificial intelligence technology to gain a deeper understanding of the relationship between the two diseases， so as to elucidate the mechanism of promoting blood circulation and removing blood stasis in preventing and treating panvascular diseases.
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Icariin,which belongs to the class of flavonoids,is the main active ingredient of the traditional tonic Chinese herb Epimedii Folium.Modern studies have shown that icariin has a wide range of effects on the male reproductive system.It has various pharmacological activities such as regulating cell proliferation and apoptosis,antioxidants,promoting testosterone secretion,improving erectile function,inhibiting prostate cancer cell migration,invasion,and regulating cell cycle.It has research value and application prospects in the field of urology and assisted reproduction.Therefore,Icariin's pharmacological effects and molecular mechanisms on the male reproductive system are reviewed in this paper combined with literature visualization analysis.It is expected to provide a theoretical basis for the therapeutic value development and application of icariin in male reproductive health.
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Approximately 25%of cancers worldwide are related to obesity and sedentary lifestyle.Changing behavior(exer-cise)may be a cost-effective means of prevention and treatment.Studies have found that exercise plays an important role in reducing cancer risk,inhibiting tumor growth,improving cancer-related quality of life,and improving the effectiveness of treatment.However,this protection mechanism is largely unclear.Clarifying the mechanism of action is essential to fully exploit the potential of exercise therapy,this article reviews the possible mechanisms for exercise to reduce the risk of cancer.
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Long non-coding RNA(lncRNA)is a type of non-protein-coding RNA with a length of at least 200 nucleotides.Ex-isting evidence shows that lncRNA affects the growth and development of humans and the occurrence of diseases through various mech-anisms,and plays an irreplaceable role in the differentiation and activation of immune cells and the development process of autoim-mune diseases.In recent years,lncRNA H19 has been found to play a unique regulatory function in pathological processes related to autoimmune diseases,such as inflammation and fibrosis.Therefore,the molecular mechanism involved in H19 is expected to become a potential target for the treatment of autoimmune diseases.In this review,we discussed the related mechanisms of H19 involved in the pathogenesis of autoimmune diseases based on the known functions of H19 and summarized the research results of H19 in several com-mon autoimmune diseases.
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Cardiovascular disease is a health hazard to humans and systolic heart failure due to myocardial infarction is a major cause of death.It was previously thought that myocardial cells of the adult mammalian heart possess a limited ability to proliferate and self-renew.However,it has been widely reported that mammals have the ability to regenerate the myocardium,which is restricted to early postnatal life,and that it is strong enough to repair damaged heart tissue.The discovery of myocardial regeneration in neonatal hearts has provided an ideal animal model to investigate the mechanisms that affect myocardial regeneration,and many mechanisms that reverse myocardial cell cycle arrest and promote myocardial regeneration have been revealed.In this article,we review the factors affecting gene expression for myocardial regeneration(e.g.,ncRNAs and transcription factors),myocardial regeneration-related signaling pathways,and the regulation of myocardial regeneration by non-myocardial cells(e.g.,extracellular matrix,immune response,and epicardium)to provide directions for achieving myocardial regeneration after myocardial injury in adult mammals.
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Objective To study the molecular mechanism of Ziyabiti tablets in the treatment of type 2 diabetes(T2DM)by network pharmacology.Methods The chemical components and related targets of Ziyabiti tablets were obtained from TCMSP,ETCM and CNKI,and the targets of T2DM were screened by OMIM and GeneCards databases.The"drug-component-target"network was built by Cytoscape 3.6.1 to screen out the core components and the core targets were screened by protein-protein interaction network.GO functional analysis and KEGG pathway enrichment analysis were performed by DAVID database.Results A total of 144 active components of Ziyabiti tablets were collected in this study,and quercetin,kaempferol,isorhamnetin and so on with higher degree values.There were 823 related targets,of which 700 were related to T2DM,including SRC,MAPK1,MAPK3,etc.GO function analysis suggested that it was related to molecular functions such as signal transduction,protein phosphorylation and protein binding.The main signaling pathways involved in KEGG pathway enrichment analysis were AGE-RAGE signaling pathways in lipid and atherosclerosis,prostate cancer,and diabetic complications.Conclusion Ziyabiti tablets have the characteristics of multi-component,multi-target,and multi-pathway synergistic intervention in the treatment of T2DM,which is mainly composed of quercetin,kaempferol,isorhamnetin and other components to regulate AGE-RAGE signaling pathways through SRC,MAPK1,MAPK3 targets.
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Cognitive dysfunction caused by blast traumatic brain injury (bTBI) is a serious neurological disease with high incidence, serious condition and poor prognosis. bTBI can lead to a series of symptoms such as short-term memory loss, inattention or multi-tasking difficulties. In severe cases, bTBI can develop into Alzheimer′s disease, which has a great impact on patients′ normal work and life. At present, researches on cognitive dysfunction caused by bTBI mainly involve model construction, pathogenesis, pathophysiological changes, diagnosis and treatment, etc., and the molecular mechanism of its occurrence remains to be further studied. Under normal physiological conditions, the release of excitatory and inhibitory neurotransmitters, the release and uptake of Ca 2+, oxidation and antioxidant systems, and the promotion and inhibition of apoptosis are in a dynamic balance. bTBI disturbs the balance, which will lead to the damage of nerve cells at the molecular level, thus resulting in the occurrence of cognitive dysfunction. To this end, the authors summarized the aspects of excitatory toxicity and Ca 2+homeostasis disorder, oxidative stress, inflammation and edema, apoptosis, etc., and reviewed the research progress on the molecular mechanism of cognitive dysfunction caused by bTBI, so as to provide a reference for the treatment and rehabilitation of cognitive dysfunction in patients with bTBI.
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ObjectiveTo explore the molecular mechanism of Qidi Tangshen prescription （QDTS） in regulating podocyte pyroptosis in diabetes nephropathy （DN）. MethodThrough in vivo experiment， db/db mice were divided into the model group， QDTS group （3.34 g·kg-1）， valsartan capsule group （10.29 mg·kg-1）， with db/m mice serving as the normal control. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and kidney pathological changes were observed. Additionally， the expression levels of pyroptosis-related indicators， including NOD-like receptor protein 3 （NLRP3）， Gasdermin D protein （GSDMD）， and interleukin-1β （IL-1β） protein， were examined. Through in vitro experiment， mouse podocytes were divided into the normal glucose group （5.5 mmol·L-1 glucose）， high glucose group （35 mmol·L-1 glucose）， DMSO group （35 mmol·L-1 glucose+200 mg·L-1 DMSO）， and QDTS group （35 mmol·L-1 glucose+200 mg·L-1 QDTS freeze-dried powder）. After 48 hours of intervention， the expression levels of NLRP3， GSDMD， and IL-1β proteins were measured in podocytes. A drug-ingredient-target-disease interaction network for QDTS in the treatment of DN was constructed by network pharmacology methods. The key signaling pathways regulating podocyte pyroptosis were analyzed， and validation was conducted through in vivo and in vitro experiments. ResultCompared with normal group， glomerular hyperplasia and glomerular basement membrane thickening were observed in model group， and some segments were accompanied by obvious podocellular process fusion. The protein expressions of NLRP3， GSDMD and IL-1β in mouse kidney were increased， the protein expressions of mitogen-activated protein kinase 14 （MAPK14）， V-Rel reticuloendotheliosis virus oncogene homology A （RELA） and Caspase-8 in mouse kidney were increased （P<0.05）. Compared with model group， kidney pathological injury of mice in QDTS group was significantly reduced， and the expressions of NLRP3， GSDMD and IL-1β in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. The protein expressions of MAPK14， RELA and Caspase-8 in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. Network pharmacology results showed that there were 16 targets for QDTS to regulate DN cell pyrodeath， among which MAPK14， RELA and Caspase-8 were the key targets. Compared with normal glucose group， the protein expressions of NLRP3， GSDMD and IL-1β in high glucose group were increased （P<0.05）， and the protein expressions of MAPK14， RELA and Caspase-8 in mouse podocytes were increased （P<0.05）. Compared with high glucose group， the expressions of NLRP3， GSDMD and IL-1β in podocytes of mice in QDTS group were decreased （P<0.05）， and the expressions of MAPK14， RELA and Caspase-8 in podocytes of mice in QDTS group were decreased （P<0.05）. ConclusionQDTS reduces damage to DN podocytes， which is associated with its regulation of the MAPK14/RELA/Caspase-8 signaling pathway and inhibition of podocyte pyroptosis.
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ObjectiveThis study aimed at conducting retrospective analysis of the clinical symptoms and genetic mutations in 20 children with Gitelman syndrome treated at the Affiliated Children′s Hospital of Nanjing Medical University from August 2015 to November 2022 and also explored the molecular mechanism of the pathogenic high-frequency mutation D486N in the Chinese population.MethodsWe collected the clinical manifestations, growth and development status, laboratory examination results, and SLC12A3 gene variations of the patients. We distinguished the wild-type and mutant SLC12A3 genes overexpressed in human embryonic kidney 293T cells (HEK293T). We used protein immunoblotting to detect the expression level of NCC, and used immunofluorescence techniques to examine the subcellular localization of NCC. In addition, we investigated the impact of the high-frequency SLC12A3 gene mutation D486N on NCC protein expression and localization.ResultsIn the 20 patients with Gitelman syndrome, all of them had hypokalemia. We indemnified twenty-six SLC12A3 gene mutations, 13 of which are missense mutation, 1 of which synonymous mutation, 1 nonsense mutation, 4 frameshift mutation, and 7 splicing site mutation. Among them, four mutations (p.T235K, c.1096-1G > A, p.A464A, and c.2660+1_2660+2insT) were novel mutations.ConclusionsWe found the preliminary evidence that the high-frequency mutation D486N in the Chinese population affected the expression of total and membrane-bound NCC protein and influenced the membrane localization of NCC protein. The findings of this study provides experimental evidence for genetic counseling, diagnosis, and treatment of Gitelman syndrome.
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Glucocorticoid-induced ocular hypertension(GIOH)is a condition characterized by elevated intraocular pressure caused by glucocorticoids. The long-term presence of GIOH may lead to optic nerve damage and visual field defects, eventually progressing to glucocorticoid-induced glaucoma(GIG), which can potentially cause blindness. Glucocorticoids primarily exert their biological effects by mediating glucocorticoid receptor(GR), while also involving factors such as transforming growth factor(TGF)-β, Wnt, and Rho in the formation of GIOH. In-depth exploration of the pathological changes and related molecular mechanisms of the trabecular meshwork in GIOH provides an important theoretical basis for understanding the pathogenesis and treatment of GIOH. Therefore, this article provides a review of the pathological changes and molecular mechanisms of the trabecular meshwork in GIOH, aiming to provide a theoretical basis for further research on the pathological mechanisms and treatment of GIOH.
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ObjectiveTo explore the mechanism of Qidi Tangshen prescription （QDTS） in alleviating podocyte injury and reducing urinary protein in diabetic nephropathy （DN）. MethodUsing network pharmacology methods， we collected the chemical components and targets of QDTS， as well as the targets related to DN. Subsequently， we constructed a "drug-ingredient-target-disease" network for QDTS in the treatment of DN to systematically elucidate the mechanism. The db/db mice were assigned into the model， QDTS （3.34 g·kg-1）， and losartan capsules （10.29 mg·kg-1） groups， and db/m mice served as the normal group. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and the urinary albumin excretion rate （UAER） and renal pathological changes were measured and observed. The expression levels of protein kinase B1 （Akt1）， hypoxia-inducible factor-1 alpha （HIF-1α）， phosphorylated B-cell lymphoma-extra-large （p-Bcl-xl）， as well as autophagy-related indicators microtubule-associated protein 1 light chain 3 （LC3）， ubiquitin-binding protein p62 （p62）， and autophagy-related gene 6 homolog （Beclin1）， were determined. Furthermore， mouse podocytes were divided into the normal glucose （5.5 mmol·L-1）， high glucose （35 mmol·L-1）， DMSO （35 mmol·L-1 glucose+200 mg·L-1 DMSO）， and QDTS （35 mmol·L-1 glucose+200 mg·L-1 QDTS freeze-dried powder） groups. After 48 h of intervention， the protein levels of Akt1， HIF-1α， p-Bcl-xl， LC3， p62， and Beclin1 in podocytes were measured. ResultQDTS had 34 active components acting on 143 targets in the treatment of DN， and 55 targets were related to autophagy， in which Akt1， HIF-1α， and Bcl-xl were the key targets. Compared with the normal group， mice in the model group exhibited significantly increased UAER， glomerular hypertrophy， deposition of blue collagen fibers， thickening of the glomerular basement membrane， and noticeable fusion of podocyte foot processes in some segments. Furthermore， the modeling up-regulated the protein levels of p-Akt1， HIF-1α， and p62 and down-regulating the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. Compared with the model group， QDTS and losartan decreased UAER （P<0.05） and alleviated the pathological damage in the renal tissue. Moreover， QDTS and losartan down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. In comparison to the normal glucose group， the high glucose group displayed up-regulated protein levels of p-Akt1， HIF-1α， and p62 and down-regulated protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. Compared with the high glucose group， QDTS down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. ConclusionQDTS alleviates podocyte damage and reduced urinary protein in DN by regulating the Akt1/HIF-1α/Bcl-xl signaling pathway， thereby enhancing podocyte autophagy.
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【Objective】 To study the relationship between ABO subtype, para-Bombay blood group and genotype, so as to explore the possible molecular mechanism of these two blood groups, and provide accurate genetic detection targets and theoretical basis for the accurate identification of ABO blood group. 【Methods】 First, the serology of 24 200 patients with blood type identification in the Ruijin Hospital from February to December in 2022 were analyzed, as well as 10 ambiguous ABO samples from other hospitals(3 were suspected ABO subtype and 7 were suspected para-Bombay blood group). Then ABO subtypes and para-Bombay blood groups were directly sequenced or post-clonal sequencing was performed to analyze ABO, FUT1 and FUT2 gene sequences. 【Results】 Among the 24 200 patients underwent blood type identification, 7 cases of ABO subtypes were detected. Among the 10 ambiguous samples sent by other hospitals, 2 of ABO subtypes, 1 of normal type A, and 7 of para-Bombay blood type were detected. In total, we identified blood types as follows: 1) 9 ABO subtypes: Ael(AEL.02/O.01.02), AelB(AEL.05/B.01), three of B3(2 of B3.03/O.01.01, 1 of B3.03/O.01.02), B(A)(BA.02/O.01.01), ABweak(A1.02/BW.07), Bweak(BW.31 /O.01.02), A2Bweak(A2.05 /BW.31); 2) 7 para-Bombay blood group: ABmh (FUT1*01N.13/FUT1*01N.13), 4 of Amh (3 of FUT1*01N.06/FUT1*01N.13, 1 of FUT1*01N.13/FUT1*01N.13); two of Bmh (FUT1*01N.06 /FUT1*01N.06, FUT1*01N.06/FUT1*01N.13), all of FUT2 of the 7 cases were FUT2*01/FUT2*01. 【Conclusion】 Clinical ABO blood group variant samples need to be identified in combination with serological and molecular biology to improve the accuracy of identification, thus providing a reference for safe blood transfusion, organ transplantation, and the prediction and prevention of fetal-maternal immune hemolytic disease.
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Pulmonary Arterial Hypertension （PAH） is a chronic progressive cardiopulmonary disease. The main pathological changes are vasoconstriction and pulmonary artery proliferative remodeling and right ventricular hypertrophy. Further exploration of the pathogenesis of PAH can reveal that its related pathways include vascular proliferation， vascular wall remodeling， oxidative stress， inflammatory response and gene regulation. Although great progress has been made in the treatment of PAH in recent years， the mortality rate is still high， current clinical treatments have not effectively improved the prognosis， and the disease has great impact on the physical， social， work and emotional aspects of patients. This article will review the latest research on the treatment of PAH， aiming to provide new clues for the clinical treatment of PAH.
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As a common clinical disease, fracture is often accompanied by pain, swelling, bleeding as well as other symptoms and has a high disability rate, even threatening life, seriously endangering patients' physical and psychological health and quality of life. Medical practitioners take many strategies for the treatment of fracture healing, including Traditional Chinese Medicine (TCM). In the early stage of fracture healing, the local fracture is often in a state of hypoxia, accompanied by the expression of hypoxia inducible factor-1α (HIF-1α), which is beneficial to wound healing. Through literature mining, we thought that hypoxia, HIF-1α and downstream factors affected the mechanism of fracture healing, as well as dominated this process. Therefore, we reviewed the local characteristics and related signaling pathways involved in the fracture healing process and summarized the intervention of TCM on these mechanisms, in order to inspirit the new strategy for fracture healing, as well as elaborate on the possible principles of TCM in treating fractures based on the HIF molecular mechanism.
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According to the World Health Organization's world report on hearing, nearly 2.5 billion people worldwide will suffer from hearing loss by 2050, which may contribute to a severe impact on individual life quality and national economies. Sensorineural hearing loss (SNHL) occurs commonly as a result of noise exposure, aging, and ototoxic drugs, and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear, which is mainly triggered by reactive oxygen species accumulation, inflammation, and mitochondrial dysfunction. Though recent advances have been made in understanding the ability of cochlear repair and regeneration, there are still no effective therapeutic drugs for SNHL. Chinese herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western medicine. Herein we present trends in research for Chinese herbal medicine for the treatment of SNHL, and elucidate their molecular mechanisms of action, to pave the way for further research and development of novel effective drugs in this field.
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Both parasitic diseases and cancers are disorders that seriously threaten human health. A strong correlation has been recently found between parasitic infections and cancers, and multiple species of parasites and their derived products have shown effective to suppress cancer development, progression and metastasis. Therefore, deciphering the interaction among parasites, cancers and hosts not only provides new insights into the development of cancer therapy, but also provides the basis for screening of parasites-derived active anticancer molecules. This review summarizes the latest advances in the anticancer activity of parasites and underlying mechanisms.
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As a widely used anti-tumor drug and anti-rheumatic drug in clinic, methotrexate (MTX) has many toxic and side effects, including gastrointestinal mucosa injury, central nervous system injury, liver and kidney function injury, etc. They often bring great trouble to the follow-up treatment of patients. The clarification of the mechanism of MTX toxicity to various organs has become the key to rescue the toxicity. The purpose of the article is to review the toxicity mechanism of MTX in various organs, so as to save the patients from the adverse reactions in clinical treatment.