Alterations in the pro-resolving lipid mediator machinery within first trimester maternal tissue: Implications in decidualization and miscarriage risk.

A pivotal event in uterine receptivity and human reproduction is the differentiation of endometrial stromal cells into decidual cells, known as decidualization. Decidualization is interlinked with its inflammatory environment. Our study aimed to investigate the presence and role of pro-resolving lipid mediators in first trimester maternal tissue. We assessed the levels of LXA4 and RvD1, along with their metabolic LOX enzymes, in elective (control) and sporadic miscarriage samples. We investigated the effects of LXA4 and RvD1 on decidualization using primary endometrial stromal cells and the immortalized endometrial stromal St-T1b cell line. The upregulation of 12- and 15-LOX expression was observed in pregnancy tissue after sporadic miscarriage, suggesting an inflammatory imbalance. Furthermore, incubation with these lipid mediators led to a decrease in decidualization biomarkers PRL and IGFBP-1, accompanied by morphological changes indicative of aberrant differentiation. The expression of LOX enzymes in decidual natural killer cells suggests their involvement in regulating the inflammatory surroundings and the extent of decidualization.

Does non-invasive brain stimulation improve spatiotemporal gait parameters in people with multiple sclerosis? A systematic review and meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease that causes progressive functional impairment, mainly in walking tasks. Noninvasive brain stimulation (NIBS) could influence the motor function and improving gait ability of patients. OBJECTIVE: The aim was to analyze the effects of NIBS (transcranial direct current stimulation [tDCS] or transcranial magnetic stimulation [TMS] on functional locomotion in people with multiple sclerosis (PwMS). METHODS: A search was conducted for randomized controlled trials published up to November 2023 comparing the application of NIBS versus a sham or control group. The primary outcome were spatiotemporal gait parameters and functional mobility. Two review authors independently assessed the risk of bias in the included studies, and we used the Grading of Recommendations Assessment, Development, and Evaluation methodology to rate the certainty of the evidence for each outcome. A meta-analysis was performed by pooling the appropriate data using RevMan Web. RESULTS: A total of four clinical trials were included for metanalysis. We observed that there is no statistically significant difference in overall effect in gait speed (MD = 0.08; 95% CI: -0.08-0.24; p = 0.32), and cadence (MD = 0.22; 95% CI: -11.54-11.98; p = 0.97%) between groups. But there was a statistically significant difference in overall effect in stride length between groups (MD:0.19; 95% CI: 0.07-0.31; p = 0.002), mainly when the intervention performed by multiple sessions and associated with motor rehabilitation (MD = 0.29; 95% CI: 0.14-0.44; p = 0.0002). CONCLUSIONS: tDCS applied by multiple session and combined with motor rehabilitation (i.e., aerobic and/or resistance training) can improve stride length in PwMS.

Repetitive peripheral sensory stimulation for motor recovery after stroke: a scoping review.

BACKGROUND AND PURPOSE: Enhancing afferent information from the paretic limb can improve post-stroke motor recovery. However, uncertainties exist regarding varied sensory peripheral neuromodulation protocols and their specific impacts. This study outlines the use of repetitive peripheral sensory stimulation (RPSS) and repetitive magnetic stimulation (rPMS) in individuals with stroke. METHODS: This scoping review was conducted according to the JBI Evidence Synthesis guidelines. We searched studies published until June 2023 on several databases using a three-step analysis and categorization of the studies: pre-analysis, exploration of the material, and data processing. RESULTS: We identified 916 studies, 52 of which were included (N = 1,125 participants). Approximately 53.84% of the participants were in the chronic phase, displaying moderate-to-severe functional impairment. Thirty-two studies used RPSS often combining it with task-oriented training, while 20 used rPMS as a standalone intervention. The RPSS primarily targeted the median and ulnar nerves, stimulating for an average of 92.78 min at an intensity that induced paresthesia. RPMS targeted the upper and lower limb paretic muscles, employing a 20 Hz frequency in most studies. The mean stimulation time was 12.74 min, with an intensity of 70% of the maximal stimulator output. Among the 114 variables analyzed in the 52 studies, 88 (77.20%) were in the "s,b" domain, with 26 (22.8%) falling under the "d" domain of the ICF. DISCUSSION AND CONCLUSION: Sensory peripheral neuromodulation protocols hold the potential for enhancing post-stroke motor recovery, yet optimal outcomes were obtained when integrated with intensive or task-oriented motor training.

Multiscale Optical Imaging Fusion for Cervical Precancer Diagnosis: Integrating Widefield Colposcopy and High-Resolution Endomicroscopy.

OBJECTIVE: Early detection and treatment of cervical precancers can prevent disease progression. However, in low-resource communities with a high incidence of cervical cancer, high equipment costs and a shortage of specialists hinder preventative strategies. This manuscript presents a low-cost multiscale in vivo optical imaging system coupled with a computer-aided diagnostic system that could enable accurate, real-time diagnosis of high-grade cervical precancers. METHODS: The system combines portable colposcopy and high-resolution endomicroscopy (HRME) to acquire spatially registered widefield and microscopy videos. A multiscale imaging fusion network (MSFN) was developed to identify cervical intraepithelial neoplasia grade 2 or more severe (CIN 2+). The MSFN automatically identifies and segments the ectocervix and lesions from colposcopy images, extracts nuclear morphology features from HRME videos, and integrates the colposcopy and HRME information. RESULTS: With a threshold value set to achieve sensitivity equal to clinical impression (0.98 [p = 1.0]), the MSFN achieved a significantly higher specificity than clinical impression (0.75 vs. 0.43, p = 0.000006). CONCLUSION: Our findings show that multiscale optical imaging of the cervix allows the highly sensitive and specific detection of high-grade precancers. SIGNIFICANCE: The multiscale imaging system and MSFN could facilitate the accurate, real-time diagnosis of cervical precancers in low-resource settings.

Decreased functional mobility in individuals with mild to moderate expanded disability status from relapsing multiple sclerosis: Analysis of the Glittre-ADL test.

INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disease that significantly limits an individual's activities of daily living (ADLs) and negatively affects their social participation as it progresses. The impact of activities and participation must be continuously assessed, and the Glittre-ADL is a validated test for MS to assess functional capacity in tasks similar to ADLs. OBJECTIVE: To evaluate whether the Glittre-ADL test is a valid method for assessing functional mobility in individuals with MS and moderate disability or those who use assistive devices. METHODS: This cross-sectional study enrolled 30 individuals in two groups: 1) MS group (n = 15); and 2) healthy control group (n = 15). The MS group underwent three functional mobility tests: 1) Glittre-ADL; 2) Timed 25-Foot Walk (T25FWT); and 3) Timed Up and Go (TUG) while the healthy group underwent only the Glittre-ADL test. RESULTS: An association was found between the Glittre-ADL time and T25FWT (r = 0.78, p < .001) and TUG (r = 0.56, p = .030) times. In the MS group, statistically significant differences were found in time (F = 2.88, p = .038) and speed (F = 5.17, p = .024) between laps. A statistically significant difference was observed between the total time in the MS and control groups (Area Under Curve - AUC: 0.982, p < .0001). A total time > 46.0s represents the reduction of functional performance during ADLs in individuals with MS (sensitivity: 93.3%; specificity: 92.2%). CONCLUSION: The Glittre-ADL test is a valid tool for assessing functional mobility in individuals with MS and mild to moderate disability (EDSS score ≤ 6.5).

Magnesium supplementation alleviates drought damage during vegetative stage of soybean plants.

Our working hypothesis was that magnesium (Mg) supplementation modulates plant performance under low water availability and improves drought tolerance in soybean genotypes. Plants of Bônus 8579, M8808 and TMG1180 genotypes were grown under field conditions and subjected to three water stress treatments (control, moderate and severe stress) and three Mg levels [0.9 (low), 1.3 (adequate) and 1.7 cmolc dm-³ (supplementation)]. After 28 days of drought imposition, the growth parameters, osmotic potential, relative water content, leaf succulence, Mg content and photosynthetic pigments were assessed. In general, drought drastically decreased the growth in all genotypes, and the reductions were intensified from moderate to severe stress. Under adequate Mg supply, TMG1180 was the most drought-tolerant genotype among the soybean plants, but Mg supplementation did not improve its tolerance. Conversely, although the M8808 genotype displayed inexpressive responses to drought under adequate Mg, the Mg-supplemented plants were found to have surprisingly better growth performance under stress compared to Bônus 8579 and TMG1180, irrespective of drought regime. The improved growth of high Mg-treated M8808-stressed plants correlated with low osmotic potential and increased relative water content, as well as shoot Mg accumulation, resulting in increased photosynthetic pigments and culminating in the highest drought tolerance. The results clearly indicate that Mg supplementation is a potential tool for alleviating water stress in M8808 soybean plants. Our findings suggest that the enhanced Mg-induced plant acclimation resulted from increased water content in plant tissues and strategic regulation of Mg content and photosynthetic pigments.

Perception of verticality in the post-COVID-19 condition correlates to infection severity.

Background: SARS-CoV-2 infection affects multiple systems, including musculoskeletal, neurological, and respiratory systems. Changes associated with physical inactivity due to prolonged hospitalization can affect the functional capacity of individuals with long coronavirus disease 2019 (COVID-19) or post-COVID-19 condition and may cause changes in some postural control functions, such as verticality. Objectives: This study aimed to evaluate the perception of verticality in individuals with long COVID. Design: Cross-sectional study. Methods: This study included 60 participants with post-COVID-19 condition divided into 2 groups: hospitalized group (n = 24), those hospitalized owing to SARS-CoV-2 infection; and non-hospitalized group (n = 36), those infected with SARS-CoV-2 but not hospitalized. All participants were examined using a post-COVID-19 functional status (PCFS), sit-to-stand test, grip strength assessment, painful and tactile sensory assessments, visual acuity assessment, and vestibular assessment. Verticality perception was evaluated using the subjective visual vertical (SVV) and subjective haptic vertical (SHV) tests. In both tests, the absolute values (positive values only) and true values (positive and negative values) were considered. To verify potential confounders that could influence the verticality of the results, logistic regression models were used for categorical variables and multiple linear regressions were used for continuous variables. For analysis between groups, the independent samples test (Mann-Whitney U test) was used. Results: There were no confounders between clinical variables and verticality in either group. There was a significant increase in absolute SVV (mean deviation [MD]: 2.83; P < .0001) and true SVV (MD: -4.18; P = .005) in the hospitalized group compared to the non-hospitalized group. Furthermore, there was a significant increase in the true SHV (MD: -3.6; P = .026) in the hospitalized group compared to that in the non-hospitalized group. Conclusion: Less accurate visual and haptic verticality perception task performance was observed in hospitalized patients with post-COVID-19 condition.

Selection of Soybean and Cowpea Cultivars with Superior Performance under Drought Using Growth and Biochemical Aspects.

Identifying cultivars of leguminous crops exhibiting drought resistance has become crucial in addressing water scarcity issues. This investigative study aimed to select soybean and cowpea cultivars with enhanced potential to grow under water restriction during the vegetative stage. Two parallel trials were conducted using seven soybean (AS3810IPRO, M8644IPRO, TMG1180RR, NS 8338IPRO, BMX81I81IPRO, M8808IPRO, and BÔNUS8579IPRO) and cowpea cultivars (Aracê, Novaera, Pajeú, Pitiúba, Tumucumaque, TVU, and Xique-xique) under four water levels (75, 60, 45, and 30% field capacity-FC) over 21 days. Growth, water content, membrane damage, photosynthetic pigments, organic compounds, and proline levels were analyzed. Drought stress significantly impacted the growth of both crops, particularly at 45 and 30% FC for soybean and 60 and 45% FC for cowpea plants. The BÔNUS8579IPRO and TMG1180RR soybean cultivars demonstrated the highest performance under drought, a response attributed to increased amino acids and proline contents, which likely help to mitigate membrane damage. For cowpea, the superior performance of the drought-stressed Xique-xique cultivar was associated with the maintenance of water content and elevated photosynthetic pigments, which contributed to the preservation of the photosynthetic efficiency and carbohydrate levels. Our findings clearly indicate promising leguminous cultivars that grow under water restriction, serving as viable alternatives for cultivating in water-limited environments.

A Direct Immunoassay Based on Surface-Enhanced Spectroscopy Using AuNP/PS-b-P2VP Nanocomposites.

A biosensor was developed for directly detecting human immunoglobulin G (IgG) and adenosine triphosphate (ATP) based on stable and reproducible gold nanoparticles/polystyrene-b-poly(2-vinylpyridine) (AuNP/PS-b-P2VP) nanocomposites. The substrates were functionalized with carboxylic acid groups for the covalent binding of anti-IgG and anti-ATP and the detection of IgG and ATP (1 to 150 µg/mL). SEM images of the nanocomposite show 17 ± 2 nm AuNP clusters adsorbed over a continuous porous PS-b-P2VP thin film. UV-VIS and SERS were used to characterize each step of the substrate functionalization and the specific interaction between anti-IgG and the targeted IgG analyte. The UV-VIS results show a redshift of the LSPR band as the AuNP surface was functionalized and SERS measurements showed consistent changes in the spectral features. Principal component analysis (PCA) was used to discriminate between samples before and after the affinity tests. Moreover, the designed biosensor proved to be sensitive to different concentrations of IgG with a limit-of-detection (LOD) down to 1 µg/mL. Moreover, the selectivity to IgG was confirmed using standard solutions of IgM as a control. Finally, ATP direct immunoassay (LOD = 1 µg/mL) has demonstrated that this nanocomposite platform can be used to detect different types of biomolecules after proper functionalization.

Protein Interactions in Rhodopseudomonas palustris TIE-1 Reveal the Molecular Basis for Resilient Photoferrotrophic Iron Oxidation.

Rhodopseudomonas palustris is an alphaproteobacterium with impressive metabolic versatility, capable of oxidizing ferrous iron to fix carbon dioxide using light energy. Photoferrotrophic iron oxidation is one of the most ancient metabolisms, sustained by the pio operon coding for three proteins: PioB and PioA, which form an outer-membrane porin-cytochrome complex that oxidizes iron outside of the cell and transfers the electrons to the periplasmic high potential iron-sulfur protein (HIPIP) PioC, which delivers them to the light-harvesting reaction center (LH-RC). Previous studies have shown that PioA deletion is the most detrimental for iron oxidation, while, the deletion of PioC resulted in only a partial loss. The expression of another periplasmic HiPIP, designated Rpal_4085, is strongly upregulated in photoferrotrophic conditions, making it a strong candidate for a PioC substitute. However, it is unable to reduce the LH-RC. In this work we used NMR spectroscopy to map the interactions between PioC, PioA, and the LH-RC, identifying the key amino acid residues involved. We also observed that PioA directly reduces the LH-RC, and this is the most likely substitute upon PioC deletion. By contrast, Rpal_4085 demontrated significant electronic and structural differences from PioC. These differences likely explain its inability to reduce the LH-RC and highlight its distinct functional role. Overall, this work reveals the functional resilience of the pio operon pathway and further highlights the use of paramagnetic NMR for understanding key biological processes.

Improving Salicornia ramosissima photochemical and biochemical resilience to extreme heatwaves through rhizosphere engineering with Plant Growth-Promoting Bacteria.

The anticipated rise in the length, frequency, and intensity of heatwaves (HW) in the Mediterranean region poses a danger to the crops, as these brief but high-intensity thermal stress events halt plant productivity. This arises the need to develop new eco-friendly sustainable strategies to overcome food demand. Halophytes such as Salicornia ramosissima appear as cash crop candidates, alongside with new biofertilization approaches using Plant Growth Promoting Bacteria (PGPB). In the present work, S. ramosissima plants exposed to heatwave (HW) treatments with and without marine PGPB inoculation is studied to evaluate the physiological responses behind eventual thermal adaptation conditions. Plants exposed to HW inoculated with ACC deaminase and IAA-producing PGPB showed a 50% reduction in the photochemical energy dissipation, when compared to their non-inoculated counterparts, indicating higher light-use efficiency. The observed concomitant increase (76-234%) in several pigments indicates improved inoculated HW-exposed individuals' light harvesting and photoprotection under stressful conditions. This reduction of the physiological stress levels in inoculated plants was also evident by the significant reduction of several antioxidant enzymes as well as of membrane lipid peroxidation products. Additionally, improved membrane stability could also be observed, through the regulation of fatty acid unsaturation levels, decreasing the excessive fluidity imposed by HW treatment. All these improved physiological traits associated with specific PGP traits highlight a key potential of the use of these PGPB consortiums as biofertilizers for S. ramosissima cash crop production in the Mediterranean, where increasing frequency in HW-events is a major drawback to plant production, even to warm-climate plants.

The endocannabinoidome in human placenta: Possible contribution to the pathogenesis of preeclampsia.

Preeclampsia (PE) was first reported thousands of years ago, yet there is still a shortage of biomarkers to determine the severity and type of PE. The importance of the expanded endocannabinoid system, or endocannabinoidome (eCBome), has emerged recently in placental physiology and pathology, though the potential alterations of the eCBome in PE have not been fully explored. Analysis by qRT-PCR using placental samples of normotensive and PE women demonstrate for the first time the presence of ABHD4, GDE1, and DAGLß in both normotensive and PE placental tissues. Interestingly, NAPE-PLD, FAAH-1, DAGLα, MAGL, and ABHD6 mRNA levels were increased in the placental tissues of PE patients. Quantification in plasma and placental tissues showed a decrease for anandamide (AEA), N-oleoylethanolamine (OEA), and N-docosahexaenoylethanolamine (DHEA) in the placenta, accompanied only by a decrease in plasma levels of AEA. In addition, a strong negative correlation was obtained between OEA and the biomarker of PE, soluble fms-like tyrosine kinase-1. Given the inflammatory nature of PE and the anti-inflammatory role of OEA and DHEA, the decrease in the local levels of these mediators may underlie the inflammatory component of this pathology. Additionally, lower AEA levels in both placenta and plasma may contribute to the atypical alterations of the spiral arteries in PE due to the vasorelaxation effects of AEA. These results add new information to the role of the eCBome members in placental development, while also pointing to a potential role as biomarkers of PE.

Improving Grapevine Heat Stress Resilience with Marine Plant Growth-Promoting Rhizobacteria Consortia.

Amid climate change, heatwave events are expected to increase in frequency and severity. As a result, yield losses in viticulture due to heatwave stress have increased over the years. As one of the most important crops in the world, an eco-friendly stress mitigation strategy is greatly needed. The present work aims to evaluate the physiological fitness improvement by two marine plant growth-promoting rhizobacteria consortia in Vitis vinifera cv. Antão Vaz under heatwave conditions. To assess the potential biophysical and biochemical thermal stress feedback amelioration, photochemical traits, pigment and fatty acid profiles, and osmotic and oxidative stress biomarkers were analysed. Bioaugmented grapevines exposed to heatwave stress presented a significantly enhanced photoprotection capability and higher thermo-stability, exhibiting a significantly lower dissipation energy flux than the non-inoculated plants. Additionally, one of the rhizobacterial consortia tested improved light-harvesting capabilities by increasing reaction centre availability and preserving photosynthetic efficiency. Rhizobacteria inoculation expressed an osmoprotectant promotion, revealed by the lower osmolyte concentration while maintaining leaf turgidity. Improved antioxidant mechanisms and membrane stability resulted in lowered lipid peroxidation product formation when compared to non-inoculated plants. Although the consortia were found to differ significantly in their effectiveness, these findings demonstrate that bioaugmentation induced significant heatwave stress tolerance and mitigation. This study revealed the promising usage of marine PGPR consortia to promote plant fitness and minimize heatwave impacts in grapevines.

Long-Term Tamoxifen Effects in the Cyclic Interaction of the Endocannabinoid and Endocrine System in the Rat Central Nervous System.

Steroid hormones can modulate the endocannabinoid system (ECS). Within the female reproductive tract, estrogen increases the expression of the cannabinoid receptors CB1 and CB2, and modifies the levels of anandamide (AEA), the major endocannabinoid, by altering the expression of both AEA synthesis (NAPE-PLD) and catabolic enzymes (FAAH). Here, we addressed the mechanisms involved in ECS fluctuations within the central nervous system and evaluated the effects of tamoxifen (TAM), a selective estrogen receptor modulator, in central AEA regulation. The current results suggest that the hypothalamic and pituitary AEA levels change differently according to the brain area and phase of the estrous cycle. In TAM-treated rats, there is a disruption of the cyclic fluctuation and reduction of the AEA levels in all brain areas. In the pituitary gland, NAPE-PLD expression increases in the metestrus phase, whereas throughout the rat cycle their expression remained constant, even upon TAM treatment. The fluctuations of pituitary AEA levels result from altered FAAH and NAPE-LPD expression. In contrast, no differences in FAAH or NAPE-PLD hypothalamic expression were observed. Overall, this study presents a broad view of the distribution and expression of ECS elements in the central nervous system and a way to suggest possible brain areas involved in the interaction of the endocannabinoid and neuroendocrine systems to induce several behavioral responses.

The effects of delta-9-tetrahydrocannabinol administration in the regulation of female rat sociosexual behaviour.

By targeting the endocannabinoid system, delta-9-tetrahydrocannabinol (THC) modulates female motivated behaviours, influenced by sex hormones. Both medial preoptic nucleus (MPN) and ventromedial nucleus of the hypothalamus (VMN) are involved in the modulation of female sexual responses. The first triggers proceptivity, whereas the ventrolateral division of the latter (VMNvl) triggers receptivity. These nuclei are modulated by glutamate, which inhibits female receptivity, and GABA, which has a dichotomous action in female sexual motivation. Here, we evaluated the action of THC on the modulation of social and sexual behaviours, on signalling pathways of MPN and VMNvl and how sex hormones influence these parameters. Young ovariectomized female rats, given sex hormones (oestradiol benzoate, EB, and progesterone, P) and THC were used for behavioural testing and for immunofluorescence analyses of vesicular glutamate transporter 2 (VGlut2) and GAD (glutamic acid decarboxylase)67 expression. Results showed that females given EB + P exhibited a higher preference for male partner, as well as higher proceptivity and a higher receptivity than control or females given only EB. Females treated with THC presented similar responses in control or EB + P female rats and even more facilitated behavioural responses in EB females than the ones that did not receive THC. Immunofluorescence results in the MPN exhibited a decreased expression of GAD67 and VGlut2 in EB + THC-treated female rats. Within VMNvl of EB-primed rats no changes in the expression of both proteins were observed after THC exposure. This study demonstrates how the possible outcomes of endocannabinoid system instability within hypothalamic neuron connectivity can modify female rat sociosexual behaviour.

Increased expression of NLRP3 inflammasome components in granulosa cells and follicular fluid interleukin(IL)-1beta and IL-18 levels in fresh IVF/ICSI cycles in women with endometriosis.

The inflammasomes are a family of recently described multi-protein cytoplasmic sensors that orchestrate the inflammatory response and participate in a variety of inflammatory conditions. We hypothesized that the activation of pyrin domain­containing protein 3 (NLRP3) inflammasome by granulosa cells (hGCs) may be activated in women with endometriosis and influence oocyte maturation and IVF outcomes. We performed a cross-sectional study to investigate the NLRP3 inflammasome status in follicular fluid (FF) and in hGCs from 44 women undergoing controlled ovarian stimulation for IVF/ICSI. Study subjects were divided into two groups according to the infertility etiology: group with tubal or male factor (control, n = 22) vs. group with endometriosis (n = 22). The FF IL-1beta and IL-18 levels in the endometriosis group were significantly higher than those in the non-endometriosis group, i.e., 5010 pg/mL and 2738 pg/mL, respectively (p < 0.05). No correlation was found between clinical pregnancy and live birth rate and analyzed inflammasome component levels (p > 0.05). In addition, the hGCs from endometriosis women demonstrated high expression of NLRP3 inflammasome at both protein and mRNA levels. Higher expression of inflammasome components within the ovary compartment may result from the exaggerated inflammatory state associated with endometriosis and thus impact the fertility of these women.

Retinoic acid (all-trans) presents antioxidant properties within human ovary and reduces progesterone production by human granulosa cells.

Both vitamin A and E support female reproduction and embryonic development. These vitamins have been associated with decreased fertility or failure to end the pregnancy in animals. An observational study was conducted on follicular fluid (FF) samples to determine the concentrations of fat-soluble vitamins of women undergoing in vitro fertilization and its correlation with assisted reproductive technology characteristics and pregnancy outcomes. Moreover, the effects of all-trans-retinoic acid (atRA) and alpha-tocopherol on granulosa cell viability, apoptosis, autophagy and hormonal production were evaluated. No association was identified between fat-soluble vitamin concentrations in FF and infertility aetiology, body mass index or woman's age. There were differences in follicular antioxidant profiles and ovarian response stimulation. In vitro evaluation of atRA and alpha-tocopherol reveals that, at physiological concentrations, both compounds may affect the viability of granulosa cells. In addition, these compounds are able to protect granulosa cells from oxidative stress, as well as to affect estradiol and progesterone production. Our data suggest that atRA and alpha-tocopherol levels should be well controlled as they may have implications in the function and viability of granulosa cells and highlights retinol as a marker of the oxidative defenses within ovary environment.

Development of a multimodal mobile colposcope for real-time cervical cancer detection.

Cervical cancer remains a leading cause of cancer death among women in low-and middle-income countries. Globally, cervical cancer prevention programs are hampered by a lack of resources, infrastructure, and personnel. We describe a multimodal mobile colposcope (MMC) designed to diagnose precancerous cervical lesions at the point-of-care without the need for biopsy. The MMC integrates two complementary imaging systems: 1) a commercially available colposcope and 2) a high speed, high-resolution, fiber-optic microendoscope (HRME). Combining these two image modalities allows, for the first time, the ability to locate suspicious cervical lesions using widefield imaging and then to obtain co-registered high-resolution images across an entire lesion. The MMC overcomes limitations of high-resolution imaging alone; widefield imaging can be used to guide the placement of the high-resolution imaging probe at clinically suspicious regions and co-registered, mosaicked high-resolution images effectively increase the field of view of high-resolution imaging. Representative data collected from patients referred for colposcopy at Barretos Cancer Hospital in Brazil, including 22,800 high resolution images and 9,900 colposcope images, illustrate the ability of the MMC to identify abnormal cervical regions, image suspicious areas with subcellular resolution, and distinguish between high-grade and low-grade dysplasia.

Unhealthy Diets Induce Distinct and Regional Effects on Intestinal Inflammatory Signalling Pathways and Long-Lasting Metabolic Dysfunction in Rats.

The intestinal epithelium is a principal site for environmental agents' detection. Several inflammation- and stress-related signalling pathways have been identified as key players in these processes. However, it is still unclear how the chronic intake of inadequate nutrients triggers inflammatory signalling pathways in different intestinal regions. We aimed to evaluate the impact of unhealthy dietary patterns, starting at a younger age, and the association with metabolic dysfunction, intestinal inflammatory response, and obesity in adulthood. A rat model was used to evaluate the effects of the consumption of sugary beverages (HSD) and a Western diet (WD), composed of ultra-processed foods. Both diets showed a positive correlation with adiposity index, but a positive correlation was found between the HSD diet and the levels of blood glucose and triglycerides, whereas the WD diet correlated positively with triglyceride levels. Moreover, a distinct inflammatory response was associated with either the WD or HSD diets. The WD induced an increase in TLR2, TLR4, and nuclear factor-kappa B (NF-κB) intestinal gene expression, with higher levels in the colon and overexpression of the inducible nitric oxide synthase. In turn, the HSD diet induced activation of the TLR2-mediated NF-κB signalling pathway in the small intestine. Altogether, these findings support the concept that early intake of unhealthy foods and nutrients are a main exogenous signal for disturbances of intestinal immune mechanisms and in a region-specific manner, ultimately leading to obesity-related disorders in later life.

The role of macrophages phenotypes in the activation of resolution pathways within human granulosa cells.

BACKGROUND: Inflammatory state within the ovaries can disrupt normal follicular dynamics, leading to reduced oocyte quality and infertility. How the production of inflammatory mediators generated by macrophages with different gene expression profile (M1 and M2) might activate inflammatory pathways, such as cyclooxygenase-2 (COX-2) and 5-, 12-, and 15-lipoxygenase (LOX), in human granulosa cells (hGCs) remains unclear. METHODS: In this study, we evaluated how M1 and M2 macrophages found in the ovaries affect the functions of hGCs isolated from women undergoing assisted reproductive technology (ART) and human ovarian granulosa COV434 cells. For this purpose, a model of interaction between hGCs and COV434 cells and conditioned media (CMs) obtained from culture of M0, M1 and M2 macrophages was established. We used real-time PCR and western blotting to detect the expression of COX-2 and 5-, 12-, and 15-LOX as biomarkers of oocyte competence. RESULTS: Our data showed that M2 macrophages with anti-inflammatory characteristics were able to significantly increase the expression of COX-2 in hGCs. We also demonstrated that M1 macrophages with pro-inflammatory characteristics were able to significantly increase the expression of 12-LOX in hGCs. However, there was no observed expression of 5-LOX and no significant alteration in the expression of 15-LOX in hGCs. Regarding COV434 cells, we found that CM from M2 macrophage resulted in an increase in COX-2, 5-LOX and 15-LOX mRNA and protein levels. No expression of 12-LOX by COV434 cells was observed when exposed to CMs from M1 and M2 macrophages. CONCLUSIONS: Our research indicated that the production of pro-resolving mediators by hGCs can, at least in part, reverse the physiological inflammation present in the ovaries.