Pre-Incisional and Multiple Intradermal Injection of N-Acetylcysteine Slightly Improves Incisional Wound Healing in an Animal Model.

The objective of this study was to investigate if delivering multiple doses of N-acetylcysteine (NAC) post-surgery in addition to pre-incisional administration significantly impacts the wound healing process in a rat model. Full-thickness skin incisions were carried out on the dorsum of 24 Sprague-Dawley rats in six locations. Fifteen minutes prior to the incision, half of the sites were treated with a control solution, with the wounds on the contralateral side treated with solutions containing 0.015%, 0.03% and 0.045% of NAC. In the case of the NAC treated group, further injections were given every 8 h for three days. On days 3, 7, 14 and 60 post-op, rats were sacrificed to gather material for the histological analysis, which included histomorphometry, collagen fiber organization analysis, immunohistochemistry and Abramov scale scoring. It was determined that scars treated with 0.015% NAC had significantly lower reepithelization than the control at day 60 post-op (p = 0.0018). Scars treated with 0.045% NAC had a significantly lower collagen fiber variance compared to 0.015% NAC at day 14 post-op (p = 0.02 and p = 0.04) and a lower mean scar width than the control at day 60 post-op (p = 0.0354 and p = 0.0224). No significant differences in the recruitment of immune cells and histological parameters were found. The results point to a limited efficacy of multiple NAC injections post-surgery in wound healing.

Anthropometry and Current Aesthetic Concept of the Lower Third of the Face and Lips in Caucasian Adult Population: A Systematic Review and Meta-Analysis.

BACKGROUND: The lack of standardization of the norms and aesthetic concept of the lower third of the face and lips creates challenges in reconstructive surgery and aesthetic procedures. A large-scale, anthropometric measurements summary poses an alternative for establishing universal patterns. METHODS: A systematic review was conducted by searching PubMed, Embase, Google Scholar and Web of Science using keywords: lip, face, aesthetics, beauty, anthropometry and Caucasian. Seventy records were included in the review and checked in detail in terms of available data. RESULTS: The study contains a meta-analysis of twelve parameters with sufficient quantitative data-lip width, nose width, facial width, lower third of the face height, midline mandible height, total height of the upper and lower lip, upper and lower vermilion height, cutaneous upper lip height and nasolabial and mentolabial angle. CONCLUSIONS: The review provides a detailed database of primary anthropometric studies of lips and perioral regions of the healthy Caucasian population. The attractiveness of the region is focused on uniformity of proportions. Notably, results acquired with different methods of measurement are not interchangeable. Despite many published anthropometric studies, systems for conducting the measurements and reporting the results are not sufficiently unified to quantitatively assess meticulous key aesthetic clinical parameters. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

VEGF and Other Gene Therapies Improve Flap Survival-A Systematic Review and Meta-Analysis of Preclinical Studies.

Surgical flaps are basic tools in reconstructive surgery. Their use may be limited by ischemia and necrosis. Few therapies address or prevent them. Genetic therapy could improve flap outcomes, but primary studies in this field present conflicting results. This systematic review and meta-analysis aimed to appraise the efficacy of external gene delivery to the flap for its survival in preclinical models. This review was registered with PROSPERO (CRD42022359982). PubMed, Embase, Web of Science, and Scopus were searched to identify studies using animal models reporting flap survival outcomes following any genetic modifications. Random-effects meta-analysis was used to calculate mean differences in flap survival with accompanying 95% CI. The risk of bias was assessed using the SYRCLE tool. Subgroup and sensitivity analyses were performed to ascertain the robustness of primary analyses, and the evidence was assessed using the GRADE approach. The initial search yielded 690 articles; 51 were eventually included, 36 of which with 1576 rats were meta-analyzed. VEGF gene delivery to different flap types significantly improved flap survival area by 15.66% (95% CI 11.80-19.52). Other interventions had smaller or less precise effects: PDGF-13.44% (95% CI 3.53-23.35); VEGF + FGF-8.64% (95% CI 6.94-10.34); HGF-5.61% (95% CI 0.43-10.78); FGF 3.84% (95% CI 1.13-6.55). Despite considerable heterogeneity, moderate risk of bias, and low quality of evidence, the efficacy of VEGF gene therapy remained significant in all sensitivity analyses. Preclinical data indicate that gene therapy is effective for increasing flap survival, but further animal studies are required for successful clinical translation.

Circulating miR-3613-5p but not miR-125b-5p, miR-199a-3p, and miR-451a are biomarkers of endometriosis.

OBJECTIVE: This study aimed to assess the utility of circulating miR-125b-5p, miR-199a-3p, miR-451a, and miR-3613-5p as biomarkers of endometriosis. STUDY DESIGN: Patients with stage III or IV of endometriosis according to the revised American Society of Reproductive Medicine (rASRM) staging classification, as well as control women, were recruited. We created a prospective study conducted on a group of 48 patients (n = 25 controls, n = 24 endometriosis) who had laparoscopic surgery. Blood samples were taken and plasma miRNA levels were measured by quantitative real-time polymerase chain reaction (RT-qPCR) and assessed with AUC and ROC curves. RESULTS: MiR-451a and miR-3613-5p were significantly decreased in the plasma of endometriosis patients. miR-451a had a receiver-operating characteristic (ROC) area under the curve 0.8283 and miR-3613-5p had a ROC area under the curve 0.7617. The concentration of circulating miR-125b-5p and miR-199-3p did not differ between endometriosis patients and controls. Plasma miRNA levels did not change with BMI, smoking status, fertility problems, or menstrual pain according to the VAS scale (p > 0.05). CONCLUSION: Circulating miR-451a and miR-3613-5p levels significantly differed between endometriosis and controls. However, the levels of miR-451a were discordant with previous studies. Therefore, miR-3613-5p may have better potential as the endometriosis biomarker. Circulating miR-125b-5p and miR-199a-3p cannot be used as reliable markers of endometriosis.

Non-Coding RNAs and Human Diseases: Current Status and Future Perspectives.

Non-coding RNAs (ncRNAs) are a family of RNA molecules that, unlike messenger RNAs, are not templates for protein synthesis but have an essential or regulatory role in this process [...].

Decreased expression of miR-23b is associated with poor survival of endometrial cancer patients.

Endometrial cancer (EC) is one of the most common types of cancer of the female reproductive system. EC is classified into two types (EC1 and EC2). MiRNAs are single-stranded RNA molecules that regulate gene expression posttranscriptionally. They have aberrant expression profiles in cancer, including EC. This study aimed to assess the level of expression of a panel of 16 miRNAs in both types of EC and healthy endometrium (HE). A total of 45 patients were enrolled into the study, 18 patients diagnosed with EC1, 12 diagnosed with EC2, and 15 HE controls. Tumor tissues or healthy endometrial tissues were dissected from archival formalin-fixed paraffin-embedded (FFPE) using laser capture microdissection (LCM). RNA was isolated from collected material and the expression of selected miRNAs was determined using the real-time qPCR. We found that miR-23b, miR-125b-5p, miR-199a-3p, miR-221-3p, and miR-451a were downregulated in EC in comparison to HE. Moreover, the expression of miR-34a-5p and miR-146-5p was higher in EC1 compared to EC2. Analysis of The Cancer Genome Atlas (TCGA) database confirmed decreased levels of miR-23b, miR-125b-5p, and miR-199a-3p in EC. Decreased miR-23b expression was associated with worse survival of EC patients.

The role of miR-200 family in the regulation of hallmarks of cancer.

MiRNAs are short non-coding RNAs that regulate gene expression post-transcriptionally contributing to the development of different diseases including cancer. The miR-200 family consists of five members, miR-200a, miR-200b, miR-200c, miR-141, and miR-429. Their expression is dysregulated in cancer tissue and their level is altered in the body fluids of cancer patients. Moreover, the levels of miR-200 family members correlate with clinical parameters such as cancer patients' survival which makes them potentially useful as diagnostic and prognostic biomarkers. MiRNAs can act as either oncomiRs or tumor suppressor miRNAs depending on the target genes and their role in the regulation of key oncogenic signaling pathways. In most types of cancer, the miR-200 family acts as tumor suppressor miRNA and regulates all features of cancer. In this review, we summarized the expression pattern of the miR-200 family in different types of cancer and their potential utility as biomarkers. Moreover, we comprehensively described the role of miR-200 family members in the regulation of all hallmarks of cancer proposed by Hanahan and Weinberg with the focus on the epithelial-mesenchymal transition, invasiveness, and metastasis of tumor cells.

Wound Healing Impairment in Type 2 Diabetes Model of Leptin-Deficient Mice-A Mechanistic Systematic Review.

Type II diabetes mellitus (T2DM) is one of the most prevalent diseases in the world, associated with diabetic foot ulcers and impaired wound healing. There is an ongoing need for interventions effective in treating these two problems. Pre-clinical studies in this field rely on adequate animal models. However, producing such a model is near-impossible given the complex and multifactorial pathogenesis of T2DM. A leptin-deficient murine model was developed in 1959 and relies on either dysfunctional leptin (ob/ob) or a leptin receptor (db/db). Though monogenic, this model has been used in hundreds of studies, including diabetic wound healing research. In this study, we systematically summarize data from over one hundred studies, which described the mechanisms underlying wound healing impairment in this model. We briefly review the wound healing dynamics, growth factors' dysregulation, angiogenesis, inflammation, the function of leptin and insulin, the role of advanced glycation end-products, extracellular matrix abnormalities, stem cells' dysregulation, and the role of non-coding RNAs. Some studies investigated novel chronic diabetes wound models, based on a leptin-deficient murine model, which was also described. We also discussed the interventions studied in vivo, which passed into human clinical trials. It is our hope that this review will help plan future research.

Evaluation of spatial PD1 and PD-L1 expression in inflammatory bowel disease samples - a pilot study.

Alterations of PD1/PD-L1 pathway may be associated with an excessive inflammatory response in the intestinal wall in inflammatory bowel diseases (IBD). To evaluate the expression of PD-1 and PD-L1 in 4 compartments of intestinal wall (mucosa, submucosa, muscularis propria and lymphatic follicles), high-resolution immunohistochemically stained slides were obtained from formalin-fixed paraffin-embedded samples of 10 Crohn's disease (CD), 9 ulcerative colitis (UC) and 10 unaffected individuals cases. The levels of expression were quantified using the QuPath software. PD-1 was detected in lymphatic follicles in affected and unaffected tissue samples and in inflammatory infiltration in IBD. There was no difference between groups neither in PD-1 overall expression nor in individual compartments, with the exception of the mucosal expression. It was higher in the mucosa of CD patients comparing to controls, however this difference was marginal (p = 0.0461). PD-L1 was expressed in endothelium and mesenteric nervous plexi, consistently in each group. There were no significant differences in PD-L1 immunoreactivity in context of histologic compartment nor clinical diagnosis. The results suggest that PD-1 and PD-L1 expression in intestinal tissue is heterogeneous in the analysed groups, thus it may be dependent on individual characteristics.

Novel diagnostic and prognostic factors for the advanced melanoma based on the glycosylation-related changes studied by biophysical profiling methods.

Melanoma is a life-threatening disease due to the early onset of metastasis and frequent resistance to the applied treatment. For now, no single histological, immunohistochemical or serological biomarker was able to provide a precise predictive value for the aggressive behavior in melanoma patients. Thus, the search for quantifying methods allowing a simultaneous diagnosis and prognosis of melanoma patients is highly desirable. By investigating specific molecular interactions with some biosensor-based techniques, one can determine novel prognostic factors for this tumor. In our previous study, we have shown the possibility of a qualitative in vitro distinguishing the commercially available melanoma cells at different progression stages based on the measurements of the lectin Concanavalin A interacting with surface glycans present on cells. Here, we present the results of the quantitative diagnostic and prognostic study of both commercial and patient-derived melanoma cells based on the evaluation of two novel factors: lectin affinity and glycan viscoelastic index obtained from the quartz crystal microbalance with dissipation monitoring (QCM-D) measurements. Two approaches to the QCM-D measurements were applied, the first uses the ability of melanoma cells to grow as a monolayer of cells on the sensor (cell-based sensors), and the second shortens the time of the analysis (suspension cell based-sensors). The results were confirmed by the complementary label-free (atomic force microscopy, AFM; and surface plasmon resonance, SPR) and labeling (lectin-ELISA; and microscale thermophoresis, MST) techniques. This new approach provides additional quantitative diagnosis and a personalized prognosis which can be done simultaneously to the traditional histopathological analysis.

Role of Lipopolysaccharide, Derived from Various Bacterial Species, in Pulpitis-A Systematic Review.

Lipopolysaccharide (LPS) is widely used for induction of inflammation in various human tissues, including dental pulp. The purpose of this study was to summarize current medical literature focusing on (1) cell types used by researchers to simulate dental pulp inflammation, (2) LPS variants utilized in experimental settings and how these choices affect the findings. Our study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched for studies reporting outcomes of lipopolysaccharide application on dental pulp cells in vitro using electronic databases: MEDLINE, Web of Science and Scopus. Having gathered data from 115 papers, we aimed to present all known effects LPS has on different cell types present in dental pulp. We focused on specific receptors and particles that are involved in molecular pathways. Our review provides an essential foundation for further research using in vitro models of pulpitis.

Biodegradable Fiducial Markers for Bimodal Near-Infrared Fluorescence- and X-ray-Based Imaging.

This study aimed to evaluate, for the first time, implantable, biodegradable fiducial markers (FMs), which were designed for bimodal, near-infrared fluorescence-based (NIRF) and X-ray-based imaging. The developed FMs had poly(l-lactide-co-caprolactone)-based core-shell structures made of radiopaque (core) and fluorescent (shell) composites with a poly(l-lactide-co-caprolactone) matrix. The approved for human use contrast agents were utilized as fillers. Indocyanine green was applied to the shell material, whereas in the core materials, iohexol and barium sulfate were compared. Moreover, the possibility of tailoring the stability of the properties of the core materials by the addition of hydroxyapatite (HAp) was examined. The performed in situ (porcine tissue) and in vivo experiment (rat model) confirmed that the developed FMs possessed pronounced contrasting properties in NIRF and X-ray imaging. The presence of HAp improved the radiopacity of FMs at the initial state. It was also proved that, in iohexol-containing FMs, the presence of HAp slightly decreased the stability of contrasting properties, while in BaSO4-containing ones, changes were less pronounced. A comprehensive material analysis explaining the differences in the stability of the contrasting properties was also presented. The tissue response around the FMs with composite cores was comparable to that of the FMs with a pristine polymeric core. The developed composite FMs did not cause serious adverse effects on the surrounding tissues even when irradiated in vivo. The developed FMs ensured good visibility for NIRF image-supported tumor surgery and the following X-ray image-guided radiotherapy. Moreover, this study replenishes a scanty report regarding similar biodegradable composite materials with a high potential for application.

A Novel and Effective Method for Human Primary Skin Melanocytes and Metastatic Melanoma Cell Isolation.

The development of an effective method of melanocyte isolation and culture is necessary for basic and clinical studies concerning skin diseases, including skin pigmentation disorders and melanoma. In this paper, we describe a novel, non-enzymatic and effective method of skin melanocyte and metastatic melanoma cell isolation and culture (along with the spontaneous spheroid creation) from skin or lymph node explants. The method is based on the selective harvesting of melanocytes and melanoma cells emigrating from the cultured explants. Thereby, isolated cells retain their natural phenotypical features, such as expression of tyrosinase and Melan-A as well as melanin production and are not contaminated by keratinocytes and fibroblasts. Such melanocyte and melanoma cell cultures may be very useful for medical and cosmetology studies, including studies of antitumor therapies.

Single Dose of N-Acetylcysteine in Local Anesthesia Increases Expression of HIF1α, MAPK1, TGFß1 and Growth Factors in Rat Wound Healing.

In this study, we aimed to investigate the influence of N-acetylcysteine (NAC) on the gene expression profile, neoangiogenesis, neutrophils and macrophages in a rat model of incisional wounds. Before creating wounds on the backs of 24 Sprague-Dawley rats, intradermal injections were made. Lidocaine-epinephrin solutions were supplemented with 0.015%, 0.03% or 0.045% solutions of NAC, or nothing (control group). Scars were harvested on the 3rd, 7th, 14th and 60th day post-surgery. We performed immunohistochemical staining in order to visualize macrophages (anti-CD68), neutrophils (anti-MPO) and newly formed blood vessels (anti-CD31). Additionally, RT-qPCR was used to measure the relative expression of 88 genes involved in the wound healing process. On the 14th day, the number of cells stained with anti-CD68 and anti-CD31 antibodies was significantly larger in the tissues treated with 0.03% NAC compared with the control. Among the selected genes, 52 were upregulated and six were downregulated at different time points. Interestingly, NAC exerted a significant effect on the expression of 45 genes 60 days after its administration. In summation, a 0.03% NAC addition to the pre-incisional anesthetic solution improves neovasculature and increases the macrophages' concentration at the wound site on the 14th day, as well as altering the expression of numerous genes that are responsible for the regenerative processes.

N-Acetylcysteine Added to Local Anesthesia Reduces Scar Area and Width in Early Wound Healing-An Animal Model Study.

The aim of the study was to evaluate if a pre-incisional N-acetylcysteine (NAC) treatment altered the process of wound healing in a rat model. The dorsal skin of 24 Sprague-Dawley rats was incised in six locations. Before the incisions were made, skin was injected either with lidocaine and epinephrine (one side) or with these agents supplemented with 0.015%, 0.03%, or 0.045% NAC (contralaterally). Photographic documentation of the wound healing process was made at 11 time points. Rats were sacrificed 3, 7, 14, or 60 days after incision to excise scars for histological analysis. They included: Abramov scale scoring, histomorphometry analysis, and collagen fiber arrangement assessment. Skin pretreated with 0.03% NAC produced the shortest scars at all analyzed time points, though this result was statistically insignificant. At this NAC concentration the scars had smaller areas on the third day and were narrower on the day 4 compared with all the other groups (p < 0.05). On day 7, at the same concentration of NAC, the scars had a higher superficial concentration index (p = 0.03) and larger dermal proliferation area (p = 0.04). NAC addition to pre-incisional anesthetic solution decreased wound size and width at an early stage of scar formation at all concentrations; however, with optimal results at 0.03% concentration.

The Role of miRNAs in the Regulation of Endometrial Cancer Invasiveness and Metastasis-A Systematic Review.

Endometrial cancer (EC) is the most common genital cancer in women with increasing death rates. MiRNAs are short non-coding RNAs that regulate gene expression on the post-transcriptional levels. Multiple studies demonstrated a fundamental role of miRNAs in the regulation of carcinogenesis. This systematic review is a comprehensive overview of the role of miRNAs in the regulation of cancer cell invasiveness and metastasis in EC. The literature was searched for studies investigating the role of miRNAs in the regulation of invasiveness and metastasis in EC. We explored PubMed, Embase, and Scopus using the following keywords: miRNA, metastasis, invasiveness, endometrial cancer. Data were collected from 163 articles that described the expression and role of 106 miRNAs in the regulation of EC invasiveness and metastasis out of which 63 were tumor suppressor miRNAs, and 38 were oncomiRNAs. Five miRNAs had a discordant role in different studies. Moreover, we identified 66 miRNAs whose expression in tumor tissue or concentration in serum correlated with at least one clinical parameter. These findings suggest a crucial role of miRNAs in the regulation of EC invasiveness and metastasis and present them as potential prognostic factors for patients with EC.

Bioactive Nanofiber-Based Conduits in a Peripheral Nerve Gap Management-An Animal Model Study.

The aim was to examine the efficiency of a scaffold made of poly (L-lactic acid)-co-poly(ϵ-caprolactone), collagen (COL), polyaniline (PANI), and enriched with adipose-derived stem cells (ASCs) as a nerve conduit in a rat model. P(LLA-CL)-COL-PANI scaffold was optimized and electrospun into a tubular-shaped structure. Adipose tissue from 10 Lewis rats was harvested for ASCs culture. A total of 28 inbred male Lewis rats underwent sciatic nerve transection and excision of a 10 mm nerve trunk fragment. In Group A, the nerve gap remained untouched; in Group B, an excised trunk was used as an autograft; in Group C, nerve stumps were secured with P(LLA-CL)-COL-PANI conduit; in Group D, P(LLA-CL)-COL-PANI conduit was enriched with ASCs. After 6 months of observation, rats were sacrificed. Gastrocnemius muscles and sciatic nerves were harvested for weight, histology analysis, and nerve fiber count analyses. Group A showed advanced atrophy of the muscle, and each intervention (B, C, D) prevented muscle mass decrease (p < 0.0001); however, ASCs addition decreased efficiency vs. autograft (p < 0.05). Nerve fiber count revealed a superior effect in the nerve fiber density observed in the groups with the use of conduit (D vs. B p < 0.0001, C vs. B p < 0.001). P(LLA-CL)-COL-PANI conduits with ASCs showed promising results in managing nerve gap by decreasing muscle atrophy.

Epithelial Cells of Deep Infiltrating Endometriosis Harbor Mutations in Cancer Driver Genes.

Endometriosis is an inflammatory condition manifested by the presence of endometrial-like tissue outside of the uterine cavity. The most common clinical presentations of endometriosis are dysmenorrhea, infertility, and severe pelvic pain. Few hypotheses attempt to explain the pathogenesis of endometriosis; however, none of the theories have been fully confirmed or considered universal. We examined somatic mutations in eutopic endometrium samples, deep endometriotic nodules and peripheral blood from 13 women with deep endometriosis of the rectovaginal space. Somatic variants were identified in laser microdissected samples using next-generation sequencing. A custom panel of 1296 cancer-related genes was employed, and selected genes representing cancer drivers and non-drivers for endometrial and ovarian cancer were thoroughly investigated. All 59 detected somatic variants were of low mutated allele frequency (<10%). In deep ectopic lesions, detected variants were significantly more often located in cancer driver genes, whereas in eutopic endometrium, there was no such distribution. Our results converge with other reports, where cancer-related mutations were found in endometriosis without cancer, particularly recurrent KRAS mutations. Genetic alterations located in ectopic endometriotic nodules could contribute to their formation; nevertheless, to better understand the pathogenesis of this disease, more research in this area must be performed.

Higher Mutation Burden in High Proliferation Compartments of Heterogeneous Melanoma Tumors.

Melanoma tumors are the most heterogeneous of all tumor types. Tumor heterogeneity results in difficulties in diagnosis and is a frequent cause of failure in treatment. Novel techniques enable accurate examination of the tumor cells, considering their heterogeneity. The study aimed to determine the somatic variations among high and low proliferating compartments of melanoma tumors. In this study, 12 archival formalin-fixed paraffin-embedded samples of previously untreated primary cutaneous melanoma were stained with Ki-67 antibody. High and low proliferating compartments from four melanoma tumors were dissected using laser-capture microdissection. DNA was isolated and analyzed quantitatively and qualitatively. Libraries for amplicon-based next-generation sequencing (NGS) were prepared using NEBNext Direct Cancer HotSpot Panel. NGS detected 206 variants in 42 genes in melanoma samples. Most of them were located within exons (135, 66%) and were predominantly non-synonymous single nucleotide variants (99, 73.3%). The analysis showed significant differences in mutational profiles between high and low proliferation compartments of melanoma tumors. Moreover, a significantly higher percentage of variants were detected only in high proliferation compartments (39%) compared to low proliferation regions (16%, p < 0.05). Our results suggest a significant functional role of genetic heterogeneity in melanoma.

Endometriosis Is Associated with Functional Polymorphism in the Promoter of Heme Oxygenase 1 (HMOX1) Gene.

Endometriosis is a common gynecological disorder characterized by the ectopic growth of endometrial-like tissue outside the uterine cavity. Etiopathogenesis of endometriosis is poorly understood; it is plausible, however, that the disease may be associated with oxidative stress related to local heme and iron metabolism. Therefore, the aim of the study was to reveal a possible association of endometriosis with a stress-inducible heme oxygenase 1 (HMOX1). For this purpose, 228 patients with clinically confirmed endometriosis and 415 control parous women from general Polish population were examined for functional -413A>T (rs2071746) single-nucleotide polymorphism (SNP) and (GT)n dinucleotide repeat length polymorphism in the promoter of HMOX1 gene. In addition, -413A>T SNP was assessed by the specific TaqMan® SNP Genotyping Assay, and (GT)n polymorphism was determined by PCR product size analysis. We found that endometriosis is associated with an increased frequency of -413A(GT)31,32 haplotype (OR (95%CI) = 1.27 (1.01-1.60), p = 0.0381) and -413A(GT)31,32 homozygous genotype [OR (95%CI) = 1.51 (1.06-2.17), p = 0.0238]. These data suggest that endometriosis is associated with functional polymorphism of HMOX1 gene, and this gene may play a part in the pathogenesis of this disorder.