Region-Specific Decellularization of Porcine Uterine Tube Extracellular Matrix: A New Approach for Reproductive Tissue-Engineering Applications.

The uterine tube extracellular matrix is a key component that regulates tubal tissue physiology, and it has a region-specific structural distribution, which is directly associated to its functions. Considering this, the application of biological matrices in culture systems is an interesting strategy to develop biomimetic tubal microenvironments and enhance their complexity. However, there are no established protocols to produce tubal biological matrices that consider the organ morphophysiology for such applications. Therefore, this study aimed to establish region-specific protocols to obtain decellularized scaffolds derived from porcine infundibulum, ampulla, and isthmus to provide suitable sources of biomaterials for tissue-engineering approaches. Porcine uterine tubes were decellularized in solutions of 0.1% SDS and 0.5% Triton X-100. The decellularization efficiency was evaluated by DAPI staining and DNA quantification. We analyzed the ECM composition and structure by optical and scanning electronic microscopy, FTIR, and Raman spectroscopy. DNA and DAPI assays validated the decellularization, presenting a significative reduction in cellular content. Structural and spectroscopy analyses revealed that the produced scaffolds remained well structured and with the ECM composition preserved. YS and HEK293 cells were used to attest cytocompatibility, allowing high cell viability rates and successful interaction with the scaffolds. These results suggest that such matrices are applicable for future biotechnological approaches in the reproductive field.

Beware of epistaxis: fatal pseudoaneurysm rupture 30 years after treatment of acromegaly.

We present a fatal complication of treatment in a patient with early-onset acromegaly, treated with two transsphenoidal operations, radiotherapy, radiosurgery and pegvisomant. He was diagnosed in his 30s, and controlled from his 40s, with stable residual tumour within the left cavernous sinus. In his 60s, 30 years after surgery/radiotherapy and 14 years after radiosurgery, he developed recurrent episodes of mild epistaxis. A week later, he presented at his local hospital's emergency department with severe epistaxis and altered consciousness. He was diagnosed with a ruptured internal carotid artery (ICA) pseudoaneurysm, but unfortunately died before treatment could be attempted.ICA pseudoaneurysms are rare complications of surgery or radiotherapy and can present with several years of delay, often with epistaxis. This case highlights the importance of life-long monitoring in patients with previous pituitary interventions and early recognition of epistaxis as a herald sign of a potentially catastrophic event, thus leading to timely treatment.

Decellularized Bovine Skeletal Muscle Scaffolds: Structural Characterization and Preliminary Cytocompatibility Evaluation.

Skeletal muscle degeneration is responsible for major mobility complications, and this muscle type has little regenerative capacity. Several biomaterials have been proposed to induce muscle regeneration and function restoration. Decellularized scaffolds present biological properties that allow efficient cell culture, providing a suitable microenvironment for artificial construct development and being an alternative for in vitro muscle culture. For translational purposes, biomaterials derived from large animals are an interesting and unexplored source for muscle scaffold production. Therefore, this study aimed to produce and characterize bovine muscle scaffolds to be applied to muscle cell 3D cultures. Bovine muscle fragments were immersed in decellularizing solutions for 7 days. Decellularization efficiency, structure, composition, and three-dimensionality were evaluated. Bovine fetal myoblasts were cultured on the scaffolds for 10 days to attest cytocompatibility. Decellularization was confirmed by DAPI staining and DNA quantification. Histological and immunohistochemical analysis attested to the preservation of main ECM components. SEM analysis demonstrated that the 3D structure was maintained. In addition, after 10 days, fetal myoblasts were able to adhere and proliferate on the scaffolds, attesting to their cytocompatibility. These data, even preliminary, infer that generated bovine muscular scaffolds were well structured, with preserved composition and allowed cell culture. This study demonstrated that biomaterials derived from bovine muscle could be used in tissue engineering.

Recombinant Human Peptide Growth Factors, Bone Morphogenetic Protein-7 (rhBMP7), and Platelet-Derived Growth Factor-BB (rhPDGF-BB) for Osteoporosis Treatment in an Oophorectomized Rat Model.

Bone morphogenetic protein (BMP) and platelet-derived growth factor (PDGF) are known to regulate/stimulate osteogenesis, playing vital roles in bone homeostasis, rendering them strong candidates for osteoporosis treatment. We evaluated the effects of recombinant human BMP-7 (rhBMP7) and PDGF-BB (rhPDGF-BB) in an oophorectomy-induced osteoporosis rat model. Forty Sprague Dawley rats underwent oophorectomy surgery; treatments commenced on the 100th day post-surgery when all animals exhibited signs of osteoporosis. These peptide growth factors were administered intraocularly (iv) once or twice a week and the animals were monitored for a total of five weeks. Two weeks after the conclusion of the treatments, the animals were euthanized and tissues were collected for assessment of alkaline phosphatase, X-ray, micro-CT, and histology. The results indicate that the most promising treatments were 20 µg/kg rhPDGF-BB + 30 µg/kg rhBMP-7 twice a week and 30 µg/kg BMP-7 twice a week, showing significant increases of 15% (p < 0.05) and 13% (p < 0.05) in bone volume fraction and 21% (p < 0.05) and 23% (p < 0.05) in trabecular number, respectively. In conclusion, rhPDGF-BB and rhBMP-7 have demonstrated the ability to increase bone volume and density in this osteoporotic animal model, establishing them as potential candidates for osteoporosis treatment.

Repurposing Kraft black Liquor as Reductant for Enhanced Lithium-Ion Battery Leaching.

The economic advantages of H2SO4 make it the acid of choice for the hydrometallurgical treatment of waste lithium-ion batteries (LIBs). However, to facilitate the full dissolution of the higher valency metal oxides present in the cathode black mass, a suitable reducing agent is required. Herein, the application of industrial black liquor (BL) obtained from the Kraft pulping for papermaking is investigated as a renewable reducing agent for the enhanced leaching of transition metals from LIB powder with H2SO4. The addition of acidified BL to H2SO4 significantly improved the leaching efficiency for a range of LIB cathode chemistries, with the strongest effect observed for manganese-rich active material. Focusing on NMC111 (LiMnxCoyNizO2) material, a linear correlation between the BL concentration and the leaching yield of Mn was obtained, with the best overall leaching efficiencies being achieved for 2.0 mol L-1 H2SO4 and 50 vol % of BL at 353 K. A quasi-total degradation of oxygenated and aromatic groups from the BL during NMC111 dissolution was observed after leaching, suggesting that these chemical groups are essential for LIB reduction. Finally, the leached transition metals could be easily recovered by pH adjustment and oxalic acid addition, closing the resource loop and fostering resource efficiency.

Successful xenotransplantation of testicular cells following fractionated chemotherapy of recipient birds.

An essential step in the success of germ cell transplantation is the preparation of the recipient's testicular environment to increase the availability of stem cell niches. However, most methods for this purpose in birds face serious limitations such as partial germ cell depletion, high toxicity and mortality, or the need to use expensive technologies. Here, we validated a simple and practical technique of transferring quail testicular cells into chicken testes depleted of endogenous spermatozoa by fractioned chemotherapy (20 mg/kg/week busulfan for 5 weeks). This protocol resulted in a very low mortality of the treated day-old chicks and, despite maintenance of androgenic activity, sperm production was decreased by 84.3% at 25 weeks of age. NANOG immunostaining revealed that very few to no germ cells were present following treatment with 20 and 40 mg/kg, respectively. RT-qPCR data also showed that c-MYC and NANOG expression declined in these treatments, but GRFα1 and BID expressions remained unaltered among groups. After xenotransplantation, quail germ cells were immunodetected in chicken testes using a species-specific antibody (QCPN), and quail ovalbumin DNA was found in seminal samples collected from chicken recipients. Together, these data confirm that fractionated administration of busulfan in hatchlings is a practical, effective, and safe protocol to prepare recipient male birds capable of supporting xenogeneic spermatogenesis.

Utilization of a Decellularized Skin Scaffold for Repair of a Cleft Palate in a Dog: A Case Report.

Cleft palates are oral deformities that mostly affect puppies. They are frequently extensive and characterized by bone and palatal mucosa malformation. This deformity is a serious condition that may result in the death of the dog, therefore surgical treatment is recommended. Tissue bioengineering has emerged as a valuable option to treat cleft palates by applying acellular biological scaffolds as grafts. This case report proposed a new approach for surgical correction of canine cleft palate through a grafting technique using a decellularized scaffold. A decellularized portion of skin was implanted to correct a large cleft palate in a 3-month-old female Pug dog. The skin fragment was obtained from a dog cadaver and a decellularization protocol was performed. Under general anesthesia, a bilateral mucoperiosteal separation of the entire length of cleft margins was performed, and the scaffold was then positioned between the tissue and the bone palate. The interaction of the grafted scaffold with the oral mucosa and palatine layers resulted in total cleft closure, without postsurgical rejection or infection, indicating the applicability of this technique in dog's cleft palate correction. This is the first reported case demonstrating this new technique, which resulted in full cleft closure and healing.

The Effect of Upper Eyelid Blepharoplasty on Corneal Tomography and Epithelial Profile.

Introduction: Upper tarsal mechanical forces influence corneal epithelial thickness profile, which could modulate corneal astigmatism. Upper eyelid blepharoplasty reduces upper tarsal strength and may have an impact on ocular surface. The aim of this study is to evaluate the effect of upper eyelid blepharoplasty on corneal epithelial thickness profile, astigmatism and aberrations. Methods: Patients with dermatochalasis underwent bilateral upper eyelid blepharoplasty. Anterior segment optical coherence tomography (AS-OCT) (Zeiss Cirrus 5000 HD-OCT) and Pentacam (Oculus, Wetzlar Germany) were performed before surgery and in the 8th postoperative week. Corneal epithelial thickness, keratometry, aberrations and asphericity were considered for statistical purposes. Only right eyes were considered. A p-value lower than 0.05 was considered significant. Results: Thirty eyes of 30 patients were included. The degree of astigmatism did not change after surgery (0.95D vs 0.83D, p=0.23). The difference between preoperative and postoperative steepest axis was 3.1° (p=0.04) with a tendency to change toward the vertical meridian. Mean epithelial thickness was higher in the inferior region both pre- and postoperatively and did not change. ET in the superior octant was lower (42 µm vs 45 µm, p<0.01) and the difference between inferior and superior octants (I-S) was higher (7 µm vs 3 µm, p<0.001) before surgery. There were no statistically significant changes in corneal aberrations (p=0.52) and asphericity (p=0.41) after surgery. Conclusion: Our results support that upper tarsus pressure influences epithelial thickness profile and, consequently, the corneal steepest keratometry. These results lead us to postulate that upper eyelid blepharoplasty may influence biometric and keratometric measurements.

Three-Dimensional Printing of Graphene Oxide/Poly-L-Lactic Acid Scaffolds Using Fischer-Koch Modeling.

Accurately printing customizable scaffolds is a challenging task because of the complexity of bone tissue composition, organization, and mechanical behavior. Graphene oxide (GO) and poly-L-lactic acid (PLLA) have drawn attention in the field of bone regeneration. However, as far as we know, the Fischer-Koch model of the GO/PLLA association for three-dimensional (3D) printing was not previously reported. This study characterizes the properties of GO/PLLA-printed scaffolds in order to achieve reproducibility of the trabecula, from virtual planning to the printed piece, as well as its response to a cell viability assay. Fourier-transform infrared and Raman spectroscopy were performed to evaluate the physicochemical properties of the nanocomposites. Cellular adhesion, proliferation, and growth on the nanocomposites were evaluated using scanning electron microscopy. Cell viability tests revealed no significant differences among different trabeculae and cell types, indicating that these nanocomposites were not cytotoxic. The Fischer Koch modeling yielded satisfactory results and can thus be used in studies directed at diverse medical applications, including bone tissue engineering and implants.

The molecular mechanisms of extracellular matrix-derived hydrogel therapy in idiopathic pulmonary fibrosis models.

Idiopathic Pulmonary Fibrosis (IPF) is a progressively debilitating lung condition characterized by oxidative stress, cell phenotype shifts, and excessive extracellular matrix (ECM) deposition. Recent studies have shown promising results using decellularized ECM-derived hydrogels produced through pepsin digestion in various lung injury models and even a human clinical trial for myocardial infarction. This study aimed to characterize the composition of ECM-derived hydrogels, assess their potential to prevent fibrosis in bleomycin-induced IPF models, and unravel their underlying molecular mechanisms of action. Porcine lungs were decellularized and pepsin-digested for 48 h. The hydrogel production process, including visualization of protein molecular weight distribution and hydrogel gelation, was characterized. Peptidomics analysis of ECM-derived hydrogel contained peptides from 224 proteins. Probable bioactive and cell-penetrating peptides, including collagen IV, laminin beta 2, and actin alpha 1, were identified. ECM-derived hydrogel treatment was administered as an early intervention to prevent fibrosis advancement in rat models of bleomycin-induced pulmonary fibrosis. ECM-derived hydrogel concentrations of 1 mg/mL and 2 mg/mL showed subtle but noticeable effects on reducing lung inflammation, oxidative damage, and protein markers related to fibrosis (e.g., alpha-smooth muscle actin, collagen I). Moreover, distinct changes were observed in macroscopic appearance, alveolar structure, collagen deposition, and protein expression between lungs that received ECM-derived hydrogel and control fibrotic lungs. Proteomic analyses revealed significant protein and gene expression changes related to cellular processes, pathways, and components involved in tissue remodeling, inflammation, and cytoskeleton regulation. RNA sequencing highlighted differentially expressed genes associated with various cellular processes, such as tissue remodeling, hormone secretion, cell chemotaxis, and cytoskeleton engagement. This study suggests that ECM-derived hydrogel treatment influence pathways associated with tissue repair, inflammation regulation, cytoskeleton reorganization, and cellular response to injury, potentially offering therapeutic benefits in preventing or mitigating lung fibrosis.

From Bariatric Surgery to Conception: The Ideal Timing to Optimize Fetal Weight.

PURPOSE: Bariatric surgery (BS) increases the risk of small for gestational age (SGA) neonates. Guidelines recommend postponing pregnancy for 12-24 months, but optimal surgery-to-conception interval (BSCI) remains uncertain. We aimed to evaluate the impact of BSCI on birth weight and SGA. MATERIALS AND METHODS: Retrospective cohort study of 42 pregnancies following BS, including Roux-en-Y gastric bypass, gastric sleeve, adjustable gastric banding and biliopancreatic diversion. Neonates were classified as SGA if birth weight < 10th percentile. Optimal BSCI was obtained from the analysis of ROC curves, and pregnancies were compared by that cut-off. RESULTS: There was a linear association between BSCI and birth weight and an inverse association with SGA, with each additional month of BSCI translating into additional 4.5 g (95%CI: 2.0-7.0) on birth weight and -6% risk of SGA (95%CI: 0.90-0.99). We established a cut-off of 24.5 months of BSCI for lower risk of SGA. Pregnancies conceived in the first 24 months had a more than tenfold increased risk of SGA (OR 12.6, 95%CI: 2.4-66.0), even when adjusted for maternal age, gestational diabetes and inadequate gestational weight gain. CONCLUSION: BSCI was associated with birth weight and SGA. Our results are in line with the recommendations of BSCI of at least 24 months to reduce the risk of SGA.

Perfusion and Ultrasonication Produce a Decellularized Porcine Whole-Ovary Scaffold with a Preserved Microarchitecture.

The application of decellularized scaffolds for artificial tissue reconstruction has been an approach with great therapeutic potential in regenerative medicine. Recently, biomimetic ovarian tissue reconstruction was proposed to reestablish ovarian endocrine functions. Despite many decellularization methods proposed, there is no established protocol for whole ovaries by detergent perfusion that is able to preserve tissue macro and microstructure with higher efficiency. This generated biomaterial may have the potential to be applied for other purposes beyond reproduction and be translated to other areas in the tissue engineering field. Therefore, this study aimed to establish and standardize a protocol for porcine ovaries' decellularization based on detergent perfusion and ultrasonication to obtain functional whole-ovary scaffolds. For that, porcine ovaries (n = 5) were perfused with detergents (0.5% SDS and 1% Triton X-100) and submitted to an ultrasonication bath to produce acellular scaffolds. The decellularization efficiency was evaluated by DAPI staining and total genomic DNA quantification. ECM morphological evaluation was performed by histological, immunohistochemistry, and ultrastructural analyses. ECM physico-chemical composition was evaluated using FTIR and Raman spectroscopy. A cytocompatibility and cell adhesion assay using murine fibroblasts was performed. Results showed that the proposed method was able to remove cellular components efficiently. There was no significant ECM component loss in relation to native tissue, and the scaffolds were cytocompatible and allowed cell attachment. In conclusion, the proposed decellularization protocol produced whole-ovaries scaffolds with preserved ECM composition and great potential for application in tissue engineering.

Placental scaffolds as a potential biological platform for embryonic stem cells differentiation into hepatic-like cells lineage: A pilot study.

Hepatic microenvironment plays an essential role in liver regeneration, providing the necessary conditions for cell proliferation, differentiation and tissue rearrangement. One of the key factors for hepatic tissue reconstruction is the extracellular matrix (ECM), which through collagenous and non-collagenous proteins provide a three-dimensional structure that confers support for cell adhesion and assists on their survival and maintenance. In this scenario, placental ECM may be eligible for hepatic tissue reconstruction, once these scaffolds hold the major components required for cell support. Therefore, this preliminary study aimed to access the possibility of mouse embryonic stem cells differentiation into hepatocyte-like cells on placental scaffolds in a three-dimensional dynamic system using a Rotary Cell Culture System. Following a four-phase differentiation protocol that simulates liver embryonic development events, the preliminary results showed that a significant quantity of cells adhered and interacted with the scaffold through outer and inner surfaces. Positive immunolabelling for alpha fetus protein and CK7 suggest presence of hepatoblast phenotype cells, and CK18 and Albumin positive immunolabelling suggest the presence of hepatocyte-like phenotype cells, demonstrating the presence of a heterogeneous population into the recellularized scaffolds. Periodic Acid Schiff-Diastase staining confirmed the presence of glycogen storage, indicating that differentiate cells acquired a hepatic-like phenotype. In conclusion, these preliminary results suggested that mouse placental scaffolds might be used as a biological platform for stem cells differentiation into hepatic-like cells and their establishment, which may be a promissing biomaterial for hepatic tissue reconstruction.

Term alpaca placenta glycosylation profile and its correlation with pregnancy maintenance and fetal survival.

Alpaca is a South American camelid, particularly present in Peruvian highlands, where oxygen concentration and atmospheric pressure are very low. Due to this fact, gestational physiology has adapted to preserve the conceptus' and mother's health. In this context, several cellular and molecular features play an essential role during and at the end of gestation. Structural carbohydrates act on maternal-fetal communication, recognize exogenous molecules, and contribute to placental barrier selectivity. Therefore, this study aimed to characterize the structural carbohydrate profiles that are present in the term alpaca placenta, kept in their natural habitat of around 4,000 m height. For this propose, 12 term alpaca placentas were collected, and the material was obtained at the time of birth from camelids raised naturally in the Peruvian highlands, in the Cusco region. All placenta samples were processed for histological analysis. A lectin histochemical investigation was performed using 13 biotinylated lectins, allowing us to determine the location of carbohydrates and their intensity on a semi-quantitative scale. Our results demonstrated that during term gestation, the epitheliochorial alpaca placenta shows a high presence of carbohydrates, particularly glucose, α-linked mannose, N-acetylglucosamine ß (GlcNAc), galactose (αGal), and N-acetylgalactosamine α (GalNAc), present in the trophoblast, amnion epithelium, and mesenchyme, as well as the presence of sialic acid residues and low affinity for fucose. In fetal blood capillaries, the presence of bi- and tri-antennary complex structures and α-linked mannose was predominated. In conclusion, we characterized the glycosylation profile in the term alpaca placenta. Based on our data, compared to those reported in the bibliography, we suggest that these carbohydrates could participate in the labor of these animals that survive in Peruvian extreme environments.

Acute kidney injury: a strong risk factor for hypoglycaemia in hospitalized patients with type 2 diabetes.

AIMS: Acute kidney injury (AKI) is highly prevalent during hospitalization of patients with type 2 diabetes (T2D). We aimed to assess the impact of AKI and its severity and duration on the risk of hypoglycaemia in hospitalized patients with T2D. METHODS: Retrospective cohort analysis of patients with T2D, admitted at a University Hospital in 2018-2019. AKI was defined as an increase in serum creatinine by ≥ 0.3 mg/dl (48 h) or ≥ 1.5 times baseline (7 days), and hypoglycaemia as blood glucose concentration < 70 mg/dl. Patients with chronic kidney disease stage ≥ 4 were excluded. We registered 239 hospitalizations with AKI and randomly selected 239 without AKI (control). Multiple logistic regression was used to adjust for confounding factors and ROC curve analysis to determine a cutoff for AKI duration. RESULTS: The risk of hypoglycaemia was higher in the AKI group (crude OR 3.6, 95%CI 1.8-9.6), even after adjusting for covariates (OR 4.2, 95%CI 1.8-9.6). Each day of AKI duration was associated with a 14% increase in the risk of hypoglycaemia (95%CI 1.1-1.2), and a cutoff of 5.5 days of AKI duration was obtained for increased risk of hypoglycaemia and mortality. AKI severity was also associated with mortality, but showed no significant association with hypoglycaemia. Patients with hypoglycaemia had 4.4 times greater risk of mortality (95%CI 2.4-8.2). CONCLUSIONS: AKI increased the risk of hypoglycaemia during hospitalization of patients with T2D, and its duration was the main risk factor. These results highlight the need for specific protocols to avoid hypoglycaemia and its burden in patients with AKI.

Biomaterials for Testicular Bioengineering: How far have we come and where do we have to go?

Traditional therapeutic interventions aim to restore male fertile potential or preserve sperm viability in severe cases, such as semen cryopreservation, testicular tissue, germ cell transplantation and testicular graft. However, these techniques demonstrate several methodological, clinical, and biological limitations, that impact in their results. In this scenario, reproductive medicine has sought biotechnological alternatives applied for infertility treatment, or to improve gamete preservation and thus increase reproductive rates in vitro and in vivo. One of the main approaches employed is the biomimetic testicular tissue reconstruction, which uses tissue-engineering principles and methodologies. This strategy pursues to mimic the testicular microenvironment, simulating physiological conditions. Such approach allows male gametes maintenance in culture or produce viable grafts that can be transplanted and restore reproductive functions. In this context, the application of several biomaterials have been proposed to be used in artificial biological systems. From synthetic polymers to decellularized matrixes, each biomaterial has advantages and disadvantages regarding its application in cell culture and tissue reconstruction. Therefore, the present review aims to list the progress that has been made and the continued challenges facing testicular regenerative medicine and the preservation of male reproductive capacity, based on the development of tissue bioengineering approaches for testicular tissue microenvironment reconstruction.

Association Between Follicle-Stimulating Hormone Receptor (FSHR) rs6166 and Estrogen Receptor 1 (ESR1) rs2234693 Polymorphisms and Polycystic Ovary Syndrome Risk, Phenotype, and Reproductive Outcomes in an Infertile Portuguese Population.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrine disorder often leading to anovulatory infertility. PCOS pathophysiology is still unclear and several potential genetic susceptibility factors have been proposed. The effect of polymorphisms in two genesrelated to follicular recruitment and development, the follicle-stimulating hormone receptor (FSHR) and the estrogen receptor 1 (ESR1), have been studied in different populations with contradictory results. AIMS: To evaluate the influence of FSHR rs6166 (c.2039A>G) and of ESR1 rs2234693 (Pvull c.453-397 T > C) polymorphisms on PCOS risk, phenotype, and response to controlled ovarian stimulation (COS). MATERIALS AND METHODS: Genotyping of the FSHR rs6166 and the ESR1 rs2234693 polymorphisms was performed in PCOS women and a control group undergoing in vitro fertilization (IVF). Demographic, clinical, and biochemical data, genotype frequency, and IVF outcomes were compared between groups. RESULTS: We evaluated 88 PCOS women and 80 controls. There was no significant difference in the genotype distribution of FSHR rs6166 polymorphism between PCOS women and controls (AA 31.8%/AS 48.9%/SS 19.3% in PCOS women vs AA 37.5%/AS 40.0%/SS 22.5% in controls; p = 0.522). The same was true for the ESR1 rs2234693 (CC 24.1%/CT 46.0%/TT 29.9% in PCOS women vs CC 18.8%/CT 48.8%/TT 32.5% in controls; p = 0.697). In PCOS women, we found higher follicle-stimulating hormone (FSH) levels on the third day of the menstrual cycle associated with the SS variant of the FSHR polymorphism (9.2 vs 6.2 ± 1.6 and 5.6 ± 1.6 mUI/mL; p = 0.011). We did not find other associations between the baseline hormonal parameters, antral follicle count, and response measures to COS with FSHR or ESR1 genotypes. We found, however, a need for higher cumulative doses of FSH for COS in patients with the SS variant of the FSHR rs6166 polymorphism (1860.5 ± 627.8 IU for SSvs 1498.1 ± 359.3 for AA and 1425.4 ± 474.8 for SA; p = 0.046 and p = 0.046). CONCLUSION: Our data suggest that in the population, FSHR rs6166and ESR1 rs2234693 polymorphisms do not influence the risk of developing PCOS nor do they influence the patient's phenotype and IVF success. However, the SS variant of the FSHR rs6166 polymorphism may be associated with FSH resistance requiring higher FSH doses for COS.

Corneal Epithelial Thickness Changes After Topical Treatment of Dry Eye Disease in Primary Sjögren Syndrome.

Purpose: To evaluate the changes on epithelial thickness before and after topical treatment in primary Sjögren syndrome-associated dry eye disease (SS-DED). Methods: This was a prospective study that included referred women with SS-DED and healthy age-matched controls. Corneal epithelial thickness was evaluated using high-definition anterior segment optical coherence tomography (Cirrus 5000 HD-OCT) in the baseline first consultation, and four weeks after treatment with preservative free 1mg/1mL sodium hyaluronate. Schirmer test 1 (ST1), tear break-up time (TBUT), tear meniscus height (TMH), SICCA Ocular Surface Score (SICCA OSS) and Ocular Surface Disease Index (OSDI) were evaluated. Statistical significance was defined as p-value <0.05. Results: The study included 40 eyes, 20 with SS-DED and 20 controls. At baseline, SS-DED patients had lower ST1 (11.1 ± 2.2mm vs 14.1 ± 3.1mm, p<0.01), faster TBUT (9.1 ± 1.8s vs 13.2 ± 1.1s, p<0.01) and lower TMH (211.2 ± 68.4 µm vs 217.2 ± 60.1µm; p<0.01) than the control group, whereas SICCA OSS and OSDI were higher (p<0.01). The superior epithelium was thinner in SS-DED group (41.1 ± 3.2 µm vs 43.1± 2.3 µm, p<0.01). After treatment, ST1, TBUT, TMH, SICCA OSS, and OSDI improved (p<0.01), and superior epithelium thickened (p<0.01) in the SS-DED group. Conclusion: Treatment with sodium hyaluronate improved ST1, TBUT, TMH, SICCA-OSS, and OSDI score. Superior epithelium tends to be thinner in SS-DED but becomes thicker with treatment. Our results seem to illustrate the morphological changes in the corneal epithelium in DED, which could be further recognized as a clinical biomarker of SS-DED.

The Canine Pancreatic Extracellular Matrix in Diabetes Mellitus and Pancreatitis: Its Essential Role and Therapeutic Perspective.

Diabetes mellitus and pancreatitis are common pancreatic diseases in dogs, affecting the endocrine and exocrine portions of the organ. Dogs have a significant role in the history of research related to genetic diseases, being considered potential models for the study of human diseases. This review discusses the importance of using the extracellular matrix of the canine pancreas as a model for the study of diabetes mellitus and pancreatitis, in addition to focusing on the importance of using extracellular matrix in new regenerative techniques, such as decellularization and recellularization. Unlike humans, rabbits, mice, and pigs, there are no reports in the literature characterizing the healthy pancreatic extracellular matrix in dogs, in addition to the absence of studies related to matrix components that are involved in triggering diabetes melittus and pancreatitis. The extracellular matrix plays the role of physical support for the cells and allows the regulation of various cellular processes. In this context, it has already been demonstrated that physiologic and pathologic pancreatic changes lead to ECM remodeling, highlighting the importance of an in-depth study of the changes associated with pancreatic diseases.

Current Trends on Bioengineering Approaches for Ovarian Microenvironment Reconstruction.

Ovarian tissue has a unique microarchitecture and a complex cellular and molecular dynamics that are essential for follicular survival and development. Due to this great complexity, several factors may lead to ovarian insufficiency, and therefore to systemic metabolic disorders and female infertility. Techniques currently used in the reproductive clinic such as oocyte cryopreservation or even ovarian tissue transplant, although effective, have several limitations, which impair their wide application. In this scenario, mimetic ovarian tissue reconstruction comes as an innovative alternative to develop new methodologies for germ cells preservation and ovarian functions restoration. The ovarian extracellular matrix (ECM) is crucial for oocyte viability maintenance, once it acts actively in folliculogenesis. One of the key components of ovarian bioengineering is biomaterials application that mimics ECM and provides conditions for cell anchorage, proliferation, and differentiation. Therefore, this review aims at describing ovarian tissue engineering approaches and listing the main limitations of current methods for preservation and reestablishment of ovarian fertility. In addition, we describe the main elements that structure this study field, highlighting the main advances and the challenges to overcome to develop innovative methodologies to be applied in reproductive medicine. Impact Statement This review presents the main advances in the application of tissue bioengineering in the ovarian tissue reconstruction to develop innovative solutions for ovarian fertility reestablishment.