Mechanism of Camellia nitidissima Chi in Treating Premature Ovarian Failure Based on Network Pharmacology and Molecular Docking

[Objectives]This study was conducted to explore active components and molecular biological mechanisms of Camellia nitidissima Chi in the treatment of premature ovarian failure(POF).[Methods]The active components and corresponding targets of C.nitidissima Chi were retrieved through literature and the TCMSP database.POF-related disease targets were identified using the OMIM and Genecards databases.A PPI network was constructed using the STRING database and Cytoscape 3.10.2.A herb-active component-target-pathway network diagram was also constructed with Cytoscape 3.10.2.The CytoNCA plugin was used to screen out the top five core targets and core active components.GO and KEGG enrichment analyses of the intersecting targets were performed using DAVID.Finally,molecular docking was conducted using Auto Dock to verify the interaction between core targets and active components,and visualization was done using PyMol.[Results]A total of 26 active components and 461 targets of C.nitidissima Chi were identified,with 154 intersecting targets related to POF.The core components of the herb included 1,1'-bi-2-naphthol,3',4-O-dimethylcedrusin,eriodictyol,quercetin,and vanillin.The PPI network revealed that the main targets were epidermal growth factor receptor(EGFR),protein kinase B1(AKT1),proto-oncogene Src(SRC),hypoxia-inducible factor 1α(HIF1A),and estrogen receptor 1(ESR1).KEGG enrichment analysis revealed 10 pathways closely related to POF,mainly involving the PI3K-Akt signaling pathway,chemical carcinogenesis-reactive oxygen species,endocrine resistance,and the HIF-1 signaling pathway.Molecular docking results showed that the core active components had strong binding activity with the targets.[Conclusions]C.nitidissima Chi has multi-component,multi-target,and multi-pathway characteristics in the comprehensive treatment of POF,providing informational support for its clinical application.

Current Status of Stem Cells in the Treatment of Premature Ovarian Failure

Premature ovarian failure (POF) is a prevalent cause of female infertility. POF features include estrogen hypofunction, amenorrhea, infertility, and high gonadotropin levels. The etiology of POF is genetic diseases, autoimmune diseases, enzyme defects and environmental factors. The development of Regenerative medicine has made stem cell and exosome (EXOs) therapy effective for POF. This review discusses POF stem cell research and development.

Recent Research Progress in Premature Ovarian Failure

Premature ovarian failure refers to ovarian function failure in women before the age of 40 years due to follicular depletion or follicular dysfunction resulting in abnormal hormone levels.The etiology and pathogenesis of premature ovarian failure may be related to genetic,immunological,medical,environmental,infectious,psychological and enzyme deficiencies.The treatment involves Western medicine,Chinese medicine,and a combination of Chinese and Western medicine,and the treatment level includes hormone level,cellular level,surgery and psychological aspect.This paper would like to review the progress of the etiology,pathogenesis and treatment of premature ovarian failure in recent years.

Intermittent spontaneous ovulation in patients with premature ovarian failure:Three case reports and review of literature

BACKGROUND Premature ovarian failure(POF)is the end-stage of a decline in ovarian function prior to the age of 40 years that involves symptoms associated with low estradiol(E2)levels and a minimal probability of pregnancy.This increases the physical and psychological burden experienced by young women of reproductive age,particularly with regards to over-diagnosis.CASE SUMMARY Here,we report three cases(29,22,and 33 years-of-age)diagnosed with POF after experiencing secondary amenorrhea for more than one year,serum levels of follicle-stimulating hormone(FSH)>40 IU/L on two occasions with an interval of more than 4 wk,and negative progesterone withdrawal tests.All three patients were intermittently administered with drugs to create an artificial cycle.During the subsequent discontinuation period,the patients experienced intermittent follicular growth and spontaneous ovulation.One patient experienced two natural pregnancies(both with embryo arrest).CONCLUSION Our findings suggest that young patients with POF can experience unpredictable and intermittent spontaneous follicular development,ovulation,and even natural pregnancy.Clinicians should provide appropriate medical guidance and individualized treatments according to fertility requirements,genetic risks and hypoestrogenic symptoms as soon as possible.

On the microstructural origin of premature failure of creep strength enhanced martensitic steels

The creep strength enhanced martensitic steels are key material for the main power generating units in ultra-supercritical plants.Studies on the evaluation of their creep rupture life show there is an overestimation of rupture life after long-term creep,which is known as premature failure.However,the microstructural origin of the premature failure remains unclear.Here in this study,we have carefully investigated the microstructural transformations and their influences on creep rupture behavior,showing that the evolution of martensite and M_(23)C_(6) carbides as well as Laves phase are responsible for the premature failure.By using multi-step TTP-LMP method,we confirmed a three-stage creep rupture behavior under different stress regions.Further quantitative analysis showed that the coarsening of M_(23)C_(6) carbides and recovery of martensite exert equal and dominant effects on the premature failure in the medium stress region,while precipitation and coarsening of Laves phase are responsible for the premature failure in the low stress region.

Human embryonic stem cell-derived mesenchymal stem cells improved premature ovarian failure

BACKGROUND Premature ovarian failure(POF)affects many adult women less than 40 years of age and leads to infertility.According to previous reports,various tissue-specific stem cells can restore ovarian function and folliculogenesis in mice with chemotherapy-induced POF.Human embryonic stem cells(ES)provide an alternative source for mesenchymal stem cells(MSCs)because of their similarities in phenotype and immunomodulatory and anti-inflammatory characteristics.Embryonic stem cell-derived mesenchymal stem cells(ES-MSCs)are attractive candidates for regenerative medicine because of their high proliferation and lack of barriers for harvesting tissue-specific MSCs.However,possible therapeutic effects and underlying mechanisms of transplanted ES-MSCs on cyclophosphamide and busulfan-induced mouse ovarian damage have not been evaluated.AIM To evaluate ES-MSCs vs bone marrow-derived mesenchymal stem cells(BMMSCs)in restoring ovarian function in a mouse model of chemotherapy-induced premature ovarian failure.METHODS Female mice received intraperitoneal injections of different doses of cyclophosphamide and busulfan to induce POF.Either human ES-MSCs or BMMSCs were transplanted into these mice.Ten days after the mice were injected with cyclophosphamide and busulfan and 4 wk after transplantation of the ESMSCs and/or BM-MSCs,we evaluated body weight,estrous cyclicity,folliclestimulating hormone and estradiol hormone concentrations and follicle count were used to evaluate the POF model and cell transplantation.Moreover,terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling,real-time PCR,Western blot analysis and immunohistochemistry and mating was used to evaluate cell transplantation.Enzyme-linked immunosorbent assay was used to analyze vascular endothelial growth factor,insulin-like growth factor 2 and hepatocyte growth factor levels in ES-MSC condition medium in order to investigate the mechanisms that underlie their function.RESULTS The human ES-MSCs significantly restored hormone secretion,survival rate and reproductive function in POF mice,which was similar to the results obtained with BM-MSCs.Gene expression analysis and the terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling assay results indicated that the ES-MSCs and/or BM-MSCs reduced apoptosis in the follicles.Notably,the transplanted mice generated new offspring.The results of different analyses showed increases in antiapoptotic and trophic proteins and genes.CONCLUSION These results suggested that transplantation of human ES-MSCs were similar to BM-MSCs in that they could restore the structure of the injured ovarian tissue and its function in chemotherapy-induced damaged POF mice and rescue fertility.The possible mechanisms of human ES-MSC were related to promotion of follicular development,ovarian secretion,fertility via a paracrine effect and ovarian cell survival.

Auricular acupoint application combined with Fujing prescription treatment for patients with premature ovarian failure

Background:To study the efficacy of Fujing prescription combined with auricular acupoint application in premature ovarian failure and its effect on hormone levels.Methods:From March 2018 to March 2020,100 patients with premature ovarian failure treated in our outpatient clinic were selected and randomly divided into a control group of 50 cases and a treatment group of 50 cases.The control group was treated with Femoston for 28 consecutive days,and the treatment group was treated with not only Femoston,but also Fujing prescription and auricular acupoint application.The patients in the two groups were treated with a 3-month course of treatment.The clinical efficacy,traditional Chinese medicine integral,serum hormone level,immune index and the occurrence of adverse reactions were compared between the two groups.Results:After treatment,the indexes of IgG,IgM and IgA in the treatment group were all increased(P<0.05 for all);compared with the control group,the incidence of adverse reactions in the treatment group was lower(P<0.05).Conclusion:The combination of Fujing prescription and auricular acupoint application in the treatment of premature ovarian failure can improve patients'clinical symptoms significantly,resulting in a decrease in follicle-stimulating hormone levels and an increase in estrogen levels.The combination of Fujing prescription and acupoint application has provided a clinical basis for the TCM treatment of premature ovarian failure.

A Preliminary Study on the Mechanism of Premature Ovarian Failure

Premature ovarian failure(POF)refers to the failure of ovaries which causes amenorrhea before the age of 40.It is characterized by primary or secondary amenorrhea along with elevated blood gonadotropin levels and decreased estrogen levels with varying degrees of low estrogen symptoms such as hot flashes and sweating,facial flushing,reduced libido,and so on.Premature ovarian failure(POF)is a common endocrine disease in gynecology.The incidence of POF is increasing year by year and the affected population increasingly involves the younger-aged groups.Its etiology is complex and diverse involving many factors such as genetics,immunity,medical treatment,environment endocrine disruptors,etc.It is also affected by long-term smoking,alcohol intake,and other behaviors which damage patients9 physical and mental health.In recent years,the effects of gene therapy in restoring ovarian function and improving fertility in animal experiments have provided a new direction for POF patients.This article discusses the etiology and possible pathogenesis of POF and BRCA from various aspects as well as summarizes the recent research status and progress of new treatment methods of POF.

Effect and Mechanism of Bushen Huoxue Recipe on Ovarian Reserve in Mice with Premature Ovarian Failure

The aim of the present study was to explore the effect and mechanism of Bushen Huoxue recipe（BHR） on ovarian reserve in mice with premature ovarian failure（POF）. Mice were divided into 3 groups： normal group, model group and BHR group. Intraperitoneal injection of cyclophosphamide was performed to create the POF model. Primordial follicular（PDF） number, ovarian wet weight, ovarian index, and estrous cycle were analyzed to evaluate the effect of BHR on POF. Meanwhile, the m RNA and protein level of Mouse Vasa Homologue（MVH） in the bone marrow, peripheral blood and ovary were detected, to explore the underlying mechanism of the treatment efficacy of BHR on ovarian reserve. By the time of BHR treatment for 28 days, BHR increased the PDF number and shortened the estrous cycle of POF mice. BHR also decreased the m RNA level of MVH in the bone marrow, and increased m RNA and protein level of MVH in the ovary of POF mice. Our results demonstrated a treatment efficacy of BHR on POF mice, and revealed that BHR might repair the dysfunction of germline stem cells in the bone marrow, and thus to improve the ovarian reserve and enhance the ovarian function of POF mice through neo-oogenesis.

Discussion on the mechanism of Erxian Decoction in the treatment of premature ovarian failure based on network pharmacology and molecular docking

Objective:To explore the mechanism of Erxian Decoction in the treatment of premature ovarian failure.Methods:Based on the method of network pharmacology and molecular docking,the active ingredients of each drug in Erxian Decoction were obtained by searching the TCMSP database;the premature ovarian failure disease targets were collected from the GeneCards,OMIM,PharmGkb and Drugbank databases,and the active ingredients and the disease gene targets were collected Click the intersection to get the predictive target of Erxian Decoction for the treatment of premature ovarian failure.Use Cytoscape 3.8.0 to construct a"drug-component-target-disease"network;construct a protein interaction network(PPI)and streamline the core network through STRING database and Cytoscape;use R Studio software to enrich the Erxiantang treatment POF with GO And KEGG pathway enrichment analysis.Use molecular docking technology to verify the results of the"drug-component-target-disease"network.Results:68 main active ingredients were screened,involving 182 gene targets,among which the main active ingredients include Quercetin,Luteolin,Kaempferol,etc.;The core target genes include RB1,TP53,FOS,CDKN1A,ESR1,AKT1,MAPK1,TNF,etc.;GO enrichment items were obtained,including the 2545 Biological Process(BP),89 Cellular Component(CC),212 Molecular Function(MF);KEGG pathways,including PI3K-Akt signaling pathway,MAPK signaling pathway,and AGE-RAGE signaling pathway in diabetic complications.The verification of the molecular docking results indicated that the main active ingredient has a good binding activity with the core target.Conclusion:This study preliminarily revealed that Erxian Decoction may play a role in the treatment of POF through multi-component,multi-target,and multi-channel synergy,which provides a reference for the next in-depth research.

Beneficial Effects of Tibolone on Sexual Dys-function in Women with Premature Ovarian Failure (POF)

Introduction: Premature Ovarian Failure (POF) is cessation of ovarian functions before the age of 40 years old with consequent cessation of menstruation. Objective of study: The aim of this study was to evaluate the association between Premature Ovarian Failure and sexual dysfunctions and outcome of management with tibolone. Patients and Methods: Thirty-one women with Premature Ovarian Failure seen at the outpatient clinic of Maternity Hospital were enrolled into the study with 31 healthy women as control group. The instrument of data collection included two types of questionnaires to assess the effect of Premature Ovarian Failure on sexuality. All the women with POF had oral tibolone 2.5 mg for at least one year and the second questionnaire and the profiles were repeated. Results: Of the 31 women with POF that presented with sexual dysfunction (SD), 27 (87.1%) complained of one or more SD domains such as reduced frequency of coitus, dyspareunia, vaginal dryness, reduced libido and general sexual satisfaction (P < 0.01), amenorrhea (P < 0.01) and hot flashes compared to 5 (16.1%) control women (P < 0.01). Administration of tibolone was associated with significant increase in frequency of coitus, reduced dyspareunia and vaginal dryness, increase libido and general satisfaction and happiness. Reduction of sexual dysfunction was predicated on the estrogenic, progestogenic and androgenic metabolite of tibolone through the reduction of serum level of FSH and LH and increased levels of estrogen and testosterone (P < 0.01). Tibolone had no adverse effect on serum lipid profile. Conclusion: Premature Ovarian Failure is associated with sexual dysfunction. Tibolone provides an effective means of treating sexual dysfunction caused by Premature Ovarian Failure.

Emotional Impacts of Premature Ovarian Failure in Kuwait

Premature Ovarian Failure (POF) is cessation of ovarian functions before the age of 40 years with consequent cessation of menstruation. The objective of study was therefore to evaluate the emotional reaction and self-efficacy of women with POF. Forty-two women confirmed to have Premature Ovarian Failure seen at the outpatient clinic of Maternity Hospital fulfilled the study criteria, were enrolled into the study. Another group of 42 healthy women formed the control group. The instrument of data collection included three types of questionnaires to assess the depth of emotional reaction to the diagnosis of POF including the subjects’ biodata, modified Health Orientation Scale (HOS) and Stanford Chronic Disease Self-Efficacy Scale. The women with POF presented at the clinic with infertility (P P P < 0.05). The diagnosis of ovarian insufficiency was a traumatic life event similar to bereavement (grieving of no obvious loss to others), with high level of anxiety, depression, fear of divorce, lower life satisfaction and impaired self-esteem. Fertility was generally of profound concern to all of them, because fertility was a societal landmark of womanhood and youth. The Stanford Chronic Self Efficacy scores were generally low (below 7) in coping with emotion reaction to loss of fertility, loss of menstruation, loss of self-esteem and other significant emotional reactions. The present study has demonstrated that Premature Ovarian Failure is associated with severe emotional distress and impaired ability to cope with them especially low self-esteem. A multidisciplinary management team is advocated for POF.

Progress in treatment of premature ovarian failure using Chinese andwestern medicine

Premature ovarian failure (POF) refers to ovarian failure in patients before the age of 40, which is manifested by aseries of symptoms such as hot flashes, hyperhidrosis, facial flushing, low sexual desire, amenorrhea, etc.Gynecological endocrine tests show that estrogen level of patients decreases while follicle stimulating hormonelevel increases, affecting pregnancy of women of childbearing age and seriously causing changes in the quality oflife of patients. The causes of POF are complex with poor therapeutic effect, which seriously endangers thephysical and mental health of patients. This paper summarized the a general description of Chinese medicine (CM)and Western medicine (WM) treating POF from the aspects of clinical application according to the existingliterature. Although WM can significantly contribute to the treatment of POF, the side effects are serious bylong-term application. CM has unique advantages, including reduced adverse reactions and higher patientcompliance. It may also fill in the shortcomings of WM in the intermittent period treatment of POF. Thecombination of Chinese and western medicine has proven to become an important direction for POF treatment.

Analysis of the relationship between liver-qi stagnation and premature ovarian failure based on exosomes

The incidence of premature ovarian failure,which is related to women’s excessive pressure and mental tension,has increased in recent years.Premature ovarian failure has become one of the diseases that seriously disturb women’s physical and mental health,and its incidence can be regarded as liver depression and qi stagnation.Patients have an increasing demand for treatment,not only for fertility with the improvement of social living standards and the development of healthcare technology.Exosomes,as small membrane vesicles containing complex RNA and proteins,have the function of mediating cell communication and transmitting information in the pathological state caused by liver-qi stagnation.Exosomes in the hypoxic microenvironment can protect cells from damage and promote the pathological process.Moreover,exosomes in an inflammatory environment can play an active anti-inflammatory role.Exosomes can reduce the apoptosis of granulosa cells by expressing miRNA and so on to restore ovarian function.The purpose of treating premature ovarian failure can be achieved in this way.This paper introduced the relationship between the three,discussed the guiding significance of Chinese medicine theories in the treatment of exosomes and premature ovarian failure,and provided new research ideas for the treatment of integrated traditional Chinese medicine and western medicine.

Studies on the correlation between human papilloma virus vaccine and premature ovarian failure

Cervical cancer is the most common malignant tumour of the female reproductive system,resulting in more than 500,000 new cases annually worldwide.In developing countries,cervical cancer ranks second in terms of cancer mortality among women.Human papilloma virus is the primary causative agent of cervical cancer,with approximately 70 percent of cervical cancers caused by high-risk types of human papilloma virus 16 and 18.There are currently three types of human papilloma virus vaccines available:bivalent,quadri-valent and nine-valent.However,in recent years,it is reported that cervical cancer vaccine can cause premature ovarian failure.Consequently,an extensive literature search to find out the correlation between human papilloma virus vaccine and premature ovarian failure became a priority.There is no sufficient evidence to support or prove that there is a link between the human papilloma virus vaccine and premature ovarian failure.Hence,the vaccine does not cause premature ovarian failure.

Research Progress on the Relationship Between Mitochondrial Dysfunction and Premature Ovarian Failure from the Perspective of TCM Treatment

Premature ovarian failure(POF)is a prevalent yet challenging condition in gynecology.Its incidence rate has been steadily rising in recent years and is trending among younger age groups.The premature failure of ovarian function,which poses a serious threat to women’s physical and mental health,has emerged as a topic of concern in current research.At present,it is believed that the causes of premature ovarian failure are multifaceted,and its pathogenesis is complex,some of which are still not well-understood.Therefore,this article discusses the research progress of the pathogenesis of premature ovarian failure caused by mitochondrial dysfunction and serves as a reference for the prevention and further research of this condition from the perspective of traditional Chinese medicine treatment.

Research Progress of Traditional Chinese Medicine in the Treatment of Premature Ovarian Failure

Premature ovarian failure refers to a disease in which women usually present with amenorrhea,infertility,decreased estrogen secretion,and increased gonadotropin before the age of 40.It seriously endangers women’s health,making them prone to various endocrine reproductive and even systemic disorders.Its pathogenesis remains unclear;however,it may be related to genetic,immune,enzyme deficiency,iatrogenic,cyclin,psychology,and other factors.Traditional Chinese medicine believes that its etiology is related to the kidney,liver,and spleen.It can be divided into kidney deficiency and liver depression syndrome,liver and kidney Yin deficiency syndrome,spleen and kidney Yang deficiency syndrome,and so on.Traditional Chinese medicine is mainly made up of oral Chinese medicine,acupuncture,and other therapies.Through literature research,this paper discusses the etiology,pathological mechanism,and treatment of premature ovarian failure in the field of traditional Chinese medicine.

Deciphering the mechanism of Liu Wei Di Huang Wan in treating premature ovarian failure:a comprehensive exploration through network pharmacology and molecular docking analysis

Premature ovarian failure(POF)is a prevalent gynecological disorder with significant implications for the physical and mental well-being of affected individuals.Liu Wei Di Huang Wan(LWDHW),a Chinese herbal compound,has demonstrated efficacy in alleviating the effects of POF.However,the underlying mechanism of action of LWDHW remains unclear.This study aimed to elucidate the potential molecular mechanism of LWDHW in treating POF using network pharmacology and molecular docking techniques.The active ingredients of LWDHW were initially screened through the TCMSP platform.At the same time,the relevant target genes associated with POF were identified using databases such as Disgenet,TTD,Drugbank,Gene Cards,OMIM,and Pharm GKB.Data analysis was conducted using the R language,Cytoscape,and STRING to construct and analyze the traditional Chinese medicine(TCM)regulatory network and protein-protein interaction(PPI)network maps.Subsequently,GO and KEGG enrichment analyses were performed using the R language.Finally,molecular docking was carried out between the protein receptors of the core genes and the corresponding small-molecule ligands.The study revealed 49 components and 189 predicted targets(after de-duplication)of LWDHW,along with 4524 targets(after de-duplication)associated with POF.Through comparative analysis,163 potential genes were identified as common targets of LWDHW and POF,participating in biological processes such as response to chemical substances,molecular function regulation,and signaling receptor binding.Key biological pathways implicated included the MAPK signaling pathway,IL-17 signaling pathway,and HIF-1 signaling pathway,among others.Molecular docking results demonstrated a robust binding ability between the core genes of LWDHW and their corresponding ingredients.In conclusion,this comprehensive analysis provided insights into the potential molecular mechanisms of LWDHW in treating POF.The identified common targets and associated pathways contributed to our understanding of how LWDHW exerted its therapeutic effects,paving the way for further research and clinical applications.It is worth noting that future studies with experimental validation and clinical trials are essential to confirm these findings and establish the safety and efficacy of LWDHW in the treatment of POF.

Interfacial microstructure evolution of 12Cr1MoV/TP347H dissimilar steel welded joints during aging

The interfacial microstructure evolution of 12Cr1MoV/TP347H dissimilar steel welded joints with a nickel-based filler metal during aging was studied in detail to elucidate the mechanism of premature failures of this kind of joints.The results showed that not only a band of granular Cr_(23)C_(6)carbides were formed along the fusion boundary in the ferritic steel during aging,but also a large number of granular or plate-like Cr_(23)C_(6)carbides,which have a cube-cube orientation relationship with the matrix,were also precipitated on the weld metal side of the fu-sion boundary,making this zone be etched more easily than the other zone and become a dark etched band.Stacking faults were found in some Cr_(23)C_(6)carbides.In the as-welded state,deformation twins were observed in the weld metal with a fully austenitic structure.The peak micro-hardness was shifted from the ferritic steel side to the weld metal side of the fusion boundary after aging and the peak value increased signific-antly.Based on the experimental results,a mechanism of premature failures of the joints was proposed.

Exposure to polycyclic aromatic hydrocarbons and risk for premature ovarian failure and reproductive hormones imbalance

Polycyclic aromatic hydrocarbons(PAHs)are a typical class of persistent organic pollutants that is ubiquitous worldwide.Previous animal studies suggested that PAHs had adverse effects on female reproduction.However,the human data regarding relationship of PAHs exposure with women reproductive health,such as ovarian dysfunction,are scarce.In this case-control study,the associations of serum levels of PAHs with the risk of premature ovarian failure(POF)and reproductive hormones in Chinese women were investigated,with recruiting 157 POF patients and 217 healthy women.The serum levels of 12 types of PAHs,as well as reproductive hormones,including follicle-stimulating hormone,luteinizing hormone and anti-mullerian hormone,were determined.In the logistic regression models,most individual PAH congeners showed significantly positive correlations with the risk of POF(p<0.05),except for fluorine and pyrene.Benzo(a)pyrene(BaP),as the most carcinogenic PAH congener,was observed to be significantly positively associated with the risk of POF.After adjustment for age,body mass index,educational levels and household income,per one-unit increase in the log-transformed BaP concentration was significantly correlated with 2.191-fold increased risk of POF(OR=2.191,95%CI:1.634-2.938,p<0.05).To the best of our knowledge,this is the first study to report an association between internal exposure levels of PAHs and the increased risk of POF in women.