Therapy For Endometriosis Research Articles

Acupuncture and Related Therapies for Endometriosis: A Network Meta-Analysis of Randomised Controlled Trials [Response to Letter

Acupuncture and Related Therapies for Endometriosis: A Network Meta-Analysis of Randomised Controlled Trials [Response to Letter

Acupuncture and Related Therapies for Endometriosis: A Network Meta-Analysis of Randomized Controlled Trials.

Acupuncture and related therapies are effective and safe ways to relieve the pain, and improve the health and quality of life in women with endometriosis-related pain. However, it is still unclear which treatment is the most effective. Our study aims to summarize the evidence and determine the most effective and safe method to treat the endometriosis. We searched PubMed, EMBASE, Cochrane Library, and Web of science, China Biology Medicine, China National Knowledge Infrastructure, Wan fang Data, Chinese Scientific Journal Database and conducted manual searches of relevant papers, summarized randomized clinical trials of acupuncture-related therapies for endometriosis from database inception to 21 April 2024. After independent literature screening and data extraction that pain VAS was selected as the primary outcome measure. The quality evaluation was conducted by Review Manager 5.4. Perform network meta-analysis (NMA) used Stata 15.0 software. Forty-two eligible trials involving six acupuncture-related interventions and 3,635 participants were included in this NMA. Pairwise meta-analyses show that combination therapy was more efficacious than western medicine and Chinese herb medicine for pain VAS scores, serum CA125 level and response rate results. The NMA estimates indicated that: for pain VAS scores, acupuncture (SMD: -2.33; 95% CI: -4.37, -0.29) and combination therapy (SMD: 1.79 95% CI: 1.21, 2.41) were superior to western medicine. For serum CA125 level, acupoint application (SMD: -11.33 95% CI: -20.28, -2.97) and combination therapy (SMD: 6.20; 95% CI: 1.60, 10.75) were associated with better efficacy when considered alongside western medicine. For response rate, combination therapy (SMD: 0.20; 95% CI: 0.14, 0.29) and auricular therapy (SMD: 8.01; 95% CI: 2.08, 45.37) were more efficacious than western medicine. The comprehensive ranking results show that acupoint catgut embedding was the best performing at lowering pain VAS scores, acupoint application was identified as the most effective in reducing serum CA125 level, and auricular therapy was ranked first in improving the response rate. Acupoint catgut embedding, auricular therapy, acupoint application and combination therapy may be the best solutions for the treatment of endometriosis. Additional trials are needed to develop higher-quality evidence and optimal regimens.

A Commentary on "Acupuncture and Related Therapies for Endometriosis: A Network Meta-Analysis of Randomised Controlled Trials" [Letter

A Commentary on "Acupuncture and Related Therapies for Endometriosis: A Network Meta-Analysis of Randomised Controlled Trials" [Letter

Self-reported Costs of Endometriosis Patients in Germany

AbstractEndometriosis patients face a significant economic burden. In addition to the directly attributable costs of the diagnosis and therapy of endometriosis, such as drug treatment and multimodal pain therapy, various indirect follow-up costs can be expected, e.g., due to incapacity for work and reduced work performance. As already reported in previous publications, endometriosis is associated with considerable costs for the health care system and society as well as for the affected women and their families.In order to measure the extent of the costs associated with endometriosis patients, 250 patients with an average age of 32.80 years were recruited via social media and interviewed about their self-financed costs as part of an online survey. The assessed direct costs comprise inpatient treatments, outpatient or pain therapy, fertility treatments, hormone therapies, prescribed and privately paid medications and aids, other therapeutic procedures, and directly attributable travel costs for endometriosis treatments.This resulted in an average cost of € 2059.55 per year. Indirect costs were calculated based on loss of income, day-to-day support, care costs, costs due to follow-up illnesses and other costs. On average, the indirect costs were € 2174.25. The average costs resulting from the survey totalled € 4233.81 per year with a standard deviation of € 8240.31.An increase of out-of-pocket costs can be assumed. This may result from an improved range of services for alternative treatment methods and an increased awareness of the need for personal investment in health. However, further health economic studies are needed to validate the results.

Targeting delivery of mifepristone to endometrial dysfunctional macrophages for endometriosis therapy

Endometriosis seriously affects 6–10 % of reproductive women globally and poses significant clinical challenges. The process of ectopic endometrial cell colonization shares similarities with cancer, and a dysfunctional immune microenvironment, characterized by non-classically polarized macrophages, plays a critical role in the progression of endometriosis. In this study, a targeted nano delivery system (BSA@Mif NPs) was developed using bovine serum albumin (BSA) as the carrier of mifepristone. The BSA@Mif NPs were utilized to selectively target M2 macrophages highly enriched in ectopic endometrial tissue via the SPARC receptor. This targeting strategy increases drug concentration at ectopic lesions while minimizing its distribution to normal tissue, thereby reducing side effects. In vitro studies demonstrated that BSA@Mif NPs not only enhanced the cellular uptake of M2-type macrophages and ectopic endometrial cells but also improved the cytotoxic effect of mifepristone on ectopic endometrial cells. Furthermore, the BSA@Mif NPs effectively induced immunogenic cell death (ICD) in ectopic endometrial cells and repolarized M2-type macrophages toward the M1 phenotype, resulting in a synergistic inhibition of ectopic endometrial cell growth. In vivo experiments revealed that BSA@Mif NPs exhibited significant therapeutic efficacy in endometriosis-bearing mice by increasing drug accumulation in the endometriotic tissues and modulating the immune microenvironment. This targeted biomimetic delivery strategy presents a promising approach for the development of endometriosis-specific therapies based on existing drugs. Statement of significanceMacrophages play an essential role in immune dysfunctional microenvironment promoting the occurrence and progression of endometriosis and can be a crucial target for developing immune microenvironment regulation strategies for the unmet long-term management of endometriosis. The albumin nanoparticles constructed based on SPARC overexpression in macrophages and endometrial cells and albumin biosafety can achieve the targeted therapy of endometriosis by increasing the passive- and active-mediated drug accumulation in ectopic endometrium and remodeling the immune microenvironment based on macrophage regulation. This study has the following implications: i) overcoming the inherent shortcomings of clinical drugs by nanotechnology is an alternative way of developing medication; ii) developing microenvironment modulation strategies based on macrophage regulation for endometriosis management is feasible.

Qualitative and Quantitative Tests on the Ingredients of Mahkota Dewa (Phaleria macrocarpa) Fruit Extract as an Alternative Therapy for Infertility in Endometriosis

Endometriosis is a gynecological disease with complaints of pain, infertility, or both, up to 35-50%. The fruit extract of Mahkota Dewa (Phaleria macrocarpa) contains antioxidants and anti-inflammatories, has anticancer prospects and is expected to have ingredients as an alternative therapy for treating infertility in endometriosis. To conduct qualitative and quantitative tests on the content of Phaleria macrocarpa fruit extract, which is expected to contain substances that act as an alternative to infertility therapy in endometriosis. Mahkota Dewa (Phaleria macrocarpa) was ripened, and its seeds were extracted using 95% ethanol twice. The results of extracts 1 and 2 were combined and then examined by Thin Layer Chromatography (TLC). The research was conducted at the Pharmacognosy-Phytochemical Laboratory, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia. Qualitative test showed that 95% ethanol extract of Phaleria macrocarpa fruit contains flavonoids, alkaloids, terpenoids, and steroids. Quantitative test using Thin Layer Chromatography (TLC) method obtained a flavonoid content of 131.51-189.89µg/ml, equivalent to quercetin, in 6 repetitions, with a wavelength of 510 nm. Phaleria macrocarpa fruit contained flavonoids, alkaloids, terpenoids and steroids. The level of steroids contained in the fruit extract of Mahkota Dewa (Phaleria macrocarpa) had not been obtained in this study.

Anxiety in Endometriosis Patients: Implications for Clinical Practice

AbstractEndometriosis is a chronic disease associated with pain that affects at least 10% of all women of reproductive age. The symptoms of endometriosis have a negative impact on quality of life; they limit the patient physically and psychologically and are the cause of significant anxiety. The aim of our study was to investigate the anxiety levels of women presenting to our specialized endometriosis outpatient clinic at the RWTH Aachen University Hospital. We sought to record their anxiety symptoms and investigate the effect of extensive counseling on anxiety in patients with endometriosis. We hypothesized that detailed counseling and the planning of multimodal endometriosis therapy would reduce anxiety.Data from 183 patients with lower abdominal pain or suspected endometriosis were analyzed. Prior to the examination, the patients completed a standardized anamnesis form including the German version of the STAI (State Trait Anxiety Inventory). The diagnosis of endometriosis was made in accordance with the recent ESHRE guideline and was based on anamnesis, gynecological examination, and ultrasound by a specialist senior physician with many years of experience in treating endometriosis.Prior to the medical examination, we observed a mean STAI-State score of 48.44 ± 11.56 and STAI-Trait score 45.68 ± 11.27. Following medical examination and planning of multimodal therapy, there was a significant decrease in the mean STAI-State score from 48.44 ± 11.56 to 42.43 ± 10.01 (p < 0.0001) and a minimal but significant decrease in the mean STAI-Trait score from 45.68 ± 11.27 to 45.01 ± 11.57 (p < 0.05).Our study showed that endometriosis is associated with high levels of anxiety. Detailed counseling and the planning of a multimodal therapy led to a significant improvement in anxiety levels.

M1 macrophages as promising agents for cell therapy of endometriosis

Endometriosis is a chronic estrogen-dependent disease characterized by the presence of endometrial glands and stroma outside their normal anatomical location. While laparoscopic removal of foci remains the gold standard therapy, it has limited efficacy and certain risks. However, cell therapy using pro-inflammatory M1 macrophages presents a promising and minimally invasive alternative for treating endometriosis. This approach showcases the potential for innovative and effective treatments for this condition. This study aims to explore the anti-endometriosis properties of M1 macrophages. A reproducible syngeneic mouse model of endometriosis was utilized, revealing that formed foci are primarily composed of macrophages with an anti-inflammatory M2 phenotype rather than M1 macrophages. To investigate further, chemically reprogrammed M1 macrophages were labeled with the membrane fluorescent tag PKH26 and administered to animals with endometriosis. Therapy resulted in a decrease in the number and size of foci, accompanied by a shift in the phenotypic composition of peritoneal macrophages. Specifically, the content of M2 macrophages decreased while that of M1 macrophages increased, resembling the composition of healthy animals. Our study conclusively demonstrates the anti-endometriosis properties of M1 macrophages, providing a strong foundation for future research in the cell therapy of endometriosis.

The role of fibrosis in endometriosis: a systematic review.

Fibrosis is an important pathological feature of endometriotic lesions of all subtypes. Fibrosis is present in and around endometriotic lesions, and a central role in its development is played by myofibroblasts, which are cells derived mainly after epithelial-to-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT). Transforming growth factor-β (TGF-β) has a key role in this myofibroblastic differentiation. Myofibroblasts deposit extracellular matrix (ECM) and have contracting abilities, leading to a stiff micro-environment. These aspects are hypothesized to be involved in the origin of endometriosis-associated pain. Additionally, similarities between endometriosis-related fibrosis and other fibrotic diseases, such as systemic sclerosis or lung fibrosis, indicate that targeting fibrosis could be a potential therapeutic strategy for non-hormonal therapy for endometriosis. This review aims to summarize the current knowledge and to highlight the knowledge gaps about the role of fibrosis in endometriosis. A comprehensive literature overview about the role of fibrosis in endometriosis can improve the efficiency of fibrosis-oriented research in endometriosis. A systematic literature search was performed in three biomedical databases using search terms for 'endometriosis', 'fibrosis', 'myofibroblasts', 'collagen', and 'α-smooth muscle actin'. Original studies were included if they reported about fibrosis and endometriosis. Both preclinical in vitro and animal studies, as well as research concerning human subjects were included. Our search yielded 3441 results, of which 142 studies were included in this review. Most studies scored a high to moderate risk of bias according to the bias assessment tools. The studies were divided in three categories: human observational studies, experimental studies with human-derived material, and animal studies. The observational studies showed details about the histologic appearance of fibrosis in endometriosis and the co-occurrence of nerves and immune cells in lesions. The in vitro studies identified several pro-fibrotic pathways in relation to endometriosis. The animal studies mainly assessed the effect of potential therapeutic strategies to halt or regress fibrosis, for example targeting platelets or mast cells. This review shows the central role of fibrosis and its main cellular driver, the myofibroblast, in endometriosis. Platelets and TGF-β have a pivotal role in pro-fibrotic signaling. The presence of nerves and neuropeptides is closely associated with fibrosis in endometriotic lesions, and is likely a cause of endometriosis-associated pain. The process of fibrotic development after EMT and FMT shares characteristics with other fibrotic diseases, so exploring similarities in endometriosis with known processes in diseases like systemic sclerosis, idiopathic pulmonary fibrosis or liver cirrhosis is relevant and a promising direction to explore new treatment strategies. The close relationship with nerves appears rather unique for endometriosis-related fibrosis and is not observed in other fibrotic diseases. N/A.

METTL14 Promotes Proliferation, Migration, and Invasion in Endometriotic Stromal Cell Growth by Activating the ZEB1/MEK/ERK Pathway.

The aim of this study was to explore the mechanism of methyltransferase-like 14 (METTL14) on human endometriotic stromal cell (ESC; HEM15A) proliferation, migration, and invasion to provide novel therapy for endometriosis (EMs). Normal human endometrial stromal cells (HESCs) and HEM15A cells were selected. Corresponding controlled experiments were performed to analyze whether overexpression of METTL14, N6-methyladenosine (m6A) methylated ZEB1 mRNA, upregulation of ZEB1, and activating the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) can affect the proliferation, migration, and invasion of HEM15A cells. Materials, Setting, and Methods: HEM15A and HESCs were cultured in vitro. HEM15A cells were treated with oe-METTL14 and oe-zinc finger E-box-binding protein 1 (ZEB1) plasmids, 3-deazaadenosine (3-DAA) and the MEK/ERK pathway inhibitor isoprenaline (ISO). After identifying HEM15A and HESCs, METTL14, ZEB1, p-ERK1/2/ERK1/2, and p-MEK/MEK levels, and cell proliferation, migration, and invasion were assessed. The modification sites of ZEB1 and m6A were predicted using SRAMP database, with an m6A modification level assessed by MeRIP. The binding of YT521-B homology domain 2 (YTHDF2) to ZEB1 messenger RNA (mRNA), and ZEB1 stability and mRNA level were tested. Compared with HESCs, METTL14 level in HEM15A was significantly reduced. METTL14 overexpression in HEM15A prominently increased its proliferation, migration, and invasion. METTL14 overexpression notably elevated m6A-methylated ZEB1 mRNA level and reduced the stability and expression of ZEB1 mRNA. Further m6A modification inhibition increased ZEB1 mRNA stability and mRNA and protein levels and decreased ZEB1 m6A modification level. ZEB1 upregulation partially reversed METTL14 overexpression-inhibited HEM15A proliferation, migration, and invasion. METTL14 inhibited the MEK/ERK signaling activation by regulating ZEB1, and the MEK/ERK signaling activation partly averted METTL14-suppressed proliferation, migration, and invasion. The effects of METTL14 on other growth aspects of HEM15A cells and the relation between ZEB1 and m6A require further investigation. METTL14 lowered ZEB1 expression by regulating ZEB1 m6A modification levels, thereby inhibiting the activation of the MEK/ERK pathway and ESC proliferation, migration, and invasion.

Altered Monocyte and Lymphocyte Phenotypes Associated with Pathogenesis and Clinical Efficacy of Progestogen Therapy for Peritoneal Endometriosis in Adolescents.

Background: Immunological imbalances characteristic of endometriosis may develop as early as the primary manifestations of the disease in adolescence. Objective: To evaluate subpopulation dynamics of monocytes and lymphocytes in peripheral blood and peritoneal fluid of adolescents with peritoneal endometriosis at diagnosis and after 1-year progestogen therapy. Methods: This study included 70 girls, 13-17 years old, diagnosed laparoscopically with peritoneal endometriosis (n = 50, main group) or paramesonephric cysts (n = 20, comparison group). Phenotypes of monocytes and lymphocytes of the blood and macrophages of the peritoneal fluid were analyzed by flow cytometry at diagnosis and during progestogen therapy. Results: Differential blood counts of CD16+ (p < 0.001) and CD86+ (p = 0.017) monocytes were identified as independent risk factors for peritoneal endometriosis in adolescents. During the treatment, cytotoxic lymphocytes CD56dimCD16bright (p = 0.049) and CD206+ monocytes (p < 0.001) significantly increased while CD163+ monocytes decreased in number (p = 0.017). The CD56dimCD16bright blood counts before (p < 0.001) and during progestogen therapy (p = 0.006), as well as CD206+ blood counts during the treatment (p = 0.038), were associated with the efficacy of pain relief after 1-year progestogen therapy. Conclusions: Adolescents with peritoneal endometriosis have altered counts of pro- and anti-inflammatory monocytes and lymphocytes both before and after 1-year progestogen therapy, correlating with treatment efficacy and justifying long-term hormonal therapy.

Calcium ascorbate loaded ultrathin ferrous sulfide nanosheets thermo-sensitive hydrogels for near-infrared light activation of synergistic endometriosis therapy

Endometriosis can cause endometrial inflammation and affect women’s reproductive health. However, it’s still challenging to develop efficient endometriosis treatment strategies until now. Herein, a novel near-infrared light (NIR)-activated hydrogel nanostructure (Vc-Ca/UFNs@Gel) with ultrathin ferrous sulfide nanosheets (UFNs) and calcium ascorbate (Vc-Ca) was developed for in situ photothermal/ferroptosis/immune synergistic endometriosis therapy. UFNs with high photothermal conversion efficiency can convert NIR into heat to achieve efficient photothermal therapy (PTT) of endometrial cells, and simultaneously melt the hydrogels to achieve the release of Vc-Ca and UFNs. Vc-Ca can greatly prevent UFNs with ultrathin nanostructure from oxidation and keep their photothermal capacity, as well as directly inhibit the proliferation of endometrial cells. UFNs with dose-dependent internalization decomposed into H2S and Fe2+ ions in endometrial cell, catalyzing the self-oxidation process of Vc-Ca to generate H2O2 and enhancing Fe2+-triggered ferroptosis of endometriosis. Interestingly, ferroptosis and PTT-triggered endometrial cell apoptosis could also induce immunogenic cell death and enhance subsequent immunotherapy. Importantly, our hydrogels can be degradable in vivo with high safety. Overall, our work proposed a novel in situ photothermal/ferroptosis/immune synergistic endometriosis therapy strategy and may have significantly potential clinical application prospects.

Follicular Fluid and Blood Monitorization of Infertility Biomarkers in Women with Endometriosis.

Infertility is recognized globally as a social disease and a growing medical condition, posing a significant challenge to modern reproductive health. Endometriosis, the third-most frequent gynecologic disorder, is one of the most common and intricate conditions that can lead to female infertility. Despite extensive research, the etiology, malignant transformation, and biological therapy of endometriosis remain unknown. Blood and follicular fluid are two matrices that have been carefully studied and can provide insights into women's health. These matrices are clinically significant because they contain metabolites closely associated with women's illness stage and reproductive outcomes. Nowadays, the application of metabolomic analysis in biological matrices may be able to predict the outcome of assisted reproductive technologies with greater precision. From a molecular viewpoint on reproductive health, we evaluate and compare the utilization of human follicular fluid and blood as matrices in analysis for diagnostic and assisted reproductive technology (ART) predictors of success for endometriosis patients. In the follicular fluid (FF), plasma, and serum of endometriosis-affected women, researchers identified dysregulations of oxidative stress, upregulation of several immune factors, and aberrations in energy metabolic pathways. The altered signatures negatively correlate with the overall oocyte and embryo quality and fertilization rate.

Targeted nanoparticles for imaging and therapy of endometriosis†.

In this brief review, we discuss our efforts to validate nanoplatforms for imaging and treatment of endometriosis. We specifically highlight our use of nonhuman primates and primate tissues in this effort. Endometriosis is a painful disorder of women and nonhuman primates where endometrium-like tissue exists outside of the uterus. There are no reliable, specific, and noninvasive diagnostic tests for endometriosis. Laparoscopic imaging remains the gold standard for identifying small endometriotic lesions in both women and monkeys. Visualizing and surgically removing microscopic lesions remains a clinical challenge. To address this challenge, we have created nanoparticle reagents that, when administered intravenously, enter endometriotic lesions both passively and by targeting endometriotic cells. The particles can carry payloads, including near-infrared fluorescent dyes and magnetic nanoparticles. These agents can be used for imaging and thermal ablation of diseased tissues. We evaluated this approach on macaque endometriotic cells, human and macaque endometrium engrafted into immunodeficient mice, in endometrium subcutaneously autografted in macaques, and in rhesus monkeys with spontaneous endometriosis. Employing these models, we report that nanoplatform-based reagents can improve imaging and provide thermal ablation of endometriotic tissues.

Learning to cope with the reality of endometriosis: A mixed-methods analysis of psychological therapy in women with endometriosis.

Despite the need and uptake of mental health support by women with endometriosis, no research to date has explored their experience of psychological therapy. We aimed to understand the factors that predict engagement in psychological therapy by Australian women with endometriosis and to qualitative explore their experience of psychological support. Mixed-methods design. A total of 200 women with self-reported endometriosis were recruited from the community. We explored; (1) the demographic and clinical predictors of engagement in psychological therapy, (2) the psychological approaches that seem most valuable to women in the management of endometriosis and (3) their experience engaging in psychological therapy for endometriosis. Nearly half of women reported to have seen a psychologist within the past year, particularly for pain. Younger age (OR, .94; 95% CI, .886-.993), depressive symptoms (OR, 1.05; 95% CI, 1.002-1.099), and working part time compared to full time (OR, 2.17, 95% CI, 1.012-4.668), increased the likelihood of engaging in psychological therapy. Template thematic analysis identified three themes; (1) endometriosis and pain have multi-faceted psychological effects, (2) psychological support is sought to adjust and live with endometriosis and (3) there are helpful and unhelpful psychological tools for women with endometriosis. Our findings support the use of psychological therapy in the management of endometriosis, and the need for psychological therapy to acknowledge the chronicity and impact of symptoms, to enlist multidisciplinary support and to consider alternative options. Further advocacy is required to educate women on the benefits of psychological therapy for endometriosis.

Interventional Hydrogel Microsphere Controlled‐Releasing Curcumin for Photothermal Therapy against Endometriosis

AbstractEndometriosis is a prevalent gynecological disorder characterized by the presence of endometrial‐like tissue outside the uterus, causing chronic pelvic pain, painful periods, and infertility. Despite the common use of hormone therapy and surgical lesion excision in its treatment, there remain significant postoperative risks and potential side effects, with a high recurrence rate. An efficient nonsurgical treatment for this condition is therefore urgently needed. In this study, an interventional hydrogel microsphere with near‐infrared (NIR)‐controlled curcumin release is developed for the non‐invasive thermal therapy of endometriosis. The hydrogel microspheres demonstrate good biocompatibility and photothermal activities, causing the death of endometrial stromal cells under NIR and controlled curcumin (Cur) release. When injected into endometriotic lesions and stimulated by NIR light, the interventional hydrogel microspheres (Cur‐FeHMPs) can raise the temperature of the endometriotic lesions to 43.65 °C, inducing endometriotic lesion elimination. Furthermore, the controlled curcumin release from the interventional hydrogel inhibits the proinflammatory environment in endometriosis. The Cur‐FeHMPs in combination with NIR present a novel strategy for endometriosis treatment.

Microfluidics-derived hierarchical microparticles for the delivery of dienogest for localized endometriosis therapy

Drug therapy is one of the most important strategies for treating gynecological diseases. Local drug delivery is promising for achieving optimal regional drug exposure, considering the complex anatomy and dynamic environment of the upper genital tract. Here, we present microparticle-based microcarriers with a hierarchical structure for localized dienogest (DNG) delivery and endometriosis treatment. The microparticles were fabricated by microfluidics and consisted of photo-crosslinked bovine serum albumin hydrogel particles (D@P-B MPs) encapsulating DNG-loaded PLGA (poly lactic-co-glycolic acid) microspheres. Such design enables the microparticles to have sustained release capacity and cell adhesion ability. Based on this, the microparticles were applied for the treatment of peritoneal endometriosis through intraperitoneal injection. The performance of the microparticles in inhibiting the growth of ectopic lesions as well as their anti-inflammatory, anti-angiogenesis, and pelvic pain-relieving effects are well demonstrated in vivo. These findings indicate that the present hierarchical microparticles are good candidates for localized treatment of endometriosis and are promising for the management of gynecological diseases. STATEMENT OF SIGNIFICANCE: We prepared photo-crosslinked bovine serum albumin hydrogel particles (D@P-B MPs) encapsulating DNG-loaded PLGA microspheres using microfluidic electrospray. Such hierarchical structure provided multiple functions of the particles as drug carriers. The hierarchical microparticles not only supported the sustained release of drugs but also provided adhesion to human ectopic endometrial stromal cells. The hierarchical microparticles represented a localized treatment method for endometriosis and is promising for the management of gynecological diseases.

Drug therapy of endometriosis

Drug therapy of endometriosis

Advances in Mesenchymal Stem Cell Research Applications for Female Infertility-Mechanisms, Efficacy Parameters, Challenges and Future Roadmap.

Infertility affects approximately 15-20% of couples globally, with female factors contributing to nearly half of cases. Conditions such as polycystic ovary syndrome, endometriosis, tubal damage and premature ovarian failure are leading causes of female infertility. Current treatments like in vitro fertilization (IVF) have limitations and risks. Mesenchymal stem cells (MSCs) have shown therapeutic potential due to their ability to differentiate, secrete trophic factors, and exhibit immunomodulatory and anti-inflammatory properties. They have been demonstrated to repair and regenerate reproductive organs in various preclinical models of infertility related conditions. MSCs have reduced endometriotic lesions, regenerated lost follicles in premature ovarian failure (POF) models, and promoted tubal repair in damage models. Some clinical and preclinical studies have reported improved outcomes with MSC therapy in endometriosis and premature ovarian failure patients. This review discusses the properties and sources of MSCs, their mechanisms of action, preclinical evidence for applications in conditions like POF, polycystic ovary syndrome (PCOS), endometriosis, Asherman syndrome, and preeclampsia, and preliminary clinical data on MSC therapy for female infertility management.

Potential mechanism of Luoshi Neiyi prescription in endometriosis based on serum pharmacochemistry and network pharmacology.

Endometriosis (EMs) is characterized by ectopic growth of active endometrial tissue outside the uterus. The Luoshi Neiyi prescription (LSNYP) has been extensively used for treating EMs in China. However, data on the active chemical components of LSNYP are insufficient, and its pharmacological mechanism in EMs treatment remains unclear. This study aimed to explore the potential mechanism of LSNYP for EMs through network pharmacology based on the components absorbed into the blood. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to analyze blood components, and a series of network pharmacology strategies were utilized to predict targets of these components and EMs. Protein-protein interaction (PPI) network analysis, component-target-disease network construction, gene ontology (GO) functional enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Additionally, molecular docking, molecular dynamics simulations, and in vitro and in vivo experiments were conducted to validate the HIF1A/EZH2/ANTXR2 pathway associated with hypoxic pathology in EMs. Thirty-four absorbed components suitable for network pharmacology analysis were identified, and core targets, such as interleukin 6, EGFR, HIF1A, and EZH2, were founded. Enrichment results indicated that treatment of EMs with LSNYP may involve the regulation of hypoxia and inflammatory-related signaling pathways and response to oxidative stress and transcription factor activity. Experimental results demonstrated that LSNYP could decrease the expression of HIF1A, ANTXR2, YAP1, CD44, and β-catenin, and increased EZH2 expression in ectopic endometrial stromal cells and endometriotic tissues. Molecular docking and molecular dynamics simulations manifested that there was stable combinatorial activity between core components and key targets of the HIF1A/EZH2/ANTXR2 pathway. LSNYP may exert pharmacological effects on EMs via the HIF1A/EZH2/ANTXR2 pathway; hence, it is a natural herb-related therapy for EMs.