A Novel Foodstuff Mixture Improves the Gut-Liver Axis in MASLD Mice and the Gut Microbiota in Overweight/Obese Patients.

Microbial community control is crucial for maintaining homeostasis of the gut-liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we show that supplementation with a mixture of Mexican foodstuffs (MexMix)-Opuntia ficus indica (nopal), Theobroma cacao (cocoa) and Acheta domesticus (crickets)-enriches several beneficial taxa in MASLD mice and overweight/obese humans. Thus, MexMix induces an important prebiotic effect. In mice, a restoration of intestinal health was observed due to the increased short-chain fatty acids (SCFAs) and intestinal crypt depth, Ocln and Cldn1 expression, and decreased Il6 and Tnfa expression. MexMix significantly reduced steatosis in the mice's liver and modified the expression of 1668 genes. By PCR, we corroborated a Tnfa and Pparg decrease, and a Cat and Sod increase. In addition, MexMix increased the hepatic NRF2 nuclear translocation and miRNA-34a, miRNA-103, and miRNA-33 decline. In overweight/obese humans, MexMix improved the body image satisfaction and reduced the fat intake. These findings indicate that this new food formulation has potential as a therapeutic approach to treat conditions associated with excessive consumption of fats and sugars.

Discovering the sensory, emotional, and interactive experiences of a place.

This article proposes a data collection technique for describing experiences of a built environment. Besides the experiences of the visual and physical aspects of the place, this technique helps describe the sensory, bodily, emotional, interactive, and social experiences occurring during the human-environment encounter. The enabling technique presented is called Reactions and Actions Description Survey (RADES). It employs 120 images depicting people going through different situations involving all the senses, showing expressions related to positive and negative emotions, and realizing varied activities. Forty-five participants visited the esplanade in the exterior of a historic building called Obispado. The case study is located on a hill and is a scenic viewpoint of Monterrey, Mexico. The participants answered the RADES and the Environmental Description Survey (ENVIDES), which focuses on describing the qualities of the place and the appraisals with which it is experienced. The comments about the experiences of the place obtained through both surveys were grouped into 133 categories. Qualitative and quantitative data about the experiences of the place were obtained through both techniques. A quantitative analysis of the data was realized since the participants not only described their experiences with words but also indicated numerically the intensity of such experiences. Spearman correlations between the experiences were calculated, and a general map of the experiences of the place was created through multidimensional scaling analysis (MDS). The study revealed the connections between the elements and qualities of the site and the views with specific positive and negative experiences occurring during the visit. Furthermore, MDS allowed the discovery of 10 dimensions of environmental experience-pleasure/displeasure, high/low arousal, dominance/submissiveness, knowing/inhabiting, environment/self, higher/lower cognition, spatiality/materiality, states/processes, natural/built, and visual/sensory. The presented techniques and the findings obtained through them can assist architects in recognizing valuable environmental features for the design of livable spaces.

Update of the guidelines for the pharmacological treatment of rheumatoid arthritis by the Mexican College of Rheumatology 2023.

OBJECTIVE: To develop updated guidelines for the pharmacological management of rheumatoid arthritis (RA). METHODS: A group of experts representative of different geographical regions and various medical services catering to the Mexican population with RA was formed. Questions based on Population, Intervention, Comparison, and Outcome (PICO) were developed, deemed clinically relevant. These questions were answered based on the results of a recent systematic literature review (SLR), and the evidence's validity was assessed using the GRADE system, considered a standard for these purposes. Subsequently, the expert group reached consensus on the direction and strength of recommendations through a multi-stage voting process. RESULTS: The updated guidelines for RA treatment stratify various therapeutic options, including different classes of DMARDs (conventional, biologicals, and JAK inhibitors), as well as NSAIDs, glucocorticoids, and analgesics. By consensus, it establishes the use of these in different subpopulations of interest among RA patients and addresses aspects related to vaccination, COVID-19, surgery, pregnancy and lactation, and others. CONCLUSIONS: This update of the Mexican guidelines for the pharmacological treatment of RA provides reference points for evidence-based decision-making, recommending patient participation in joint decision-making to achieve the greatest benefit for our patients. It also establishes recommendations for managing a variety of relevant conditions affecting our patients.

Atmospheric black carbon observations and its valley-mountain dynamics: Eastern cordillera of the central Andes of Peru.

Glacial bodies in the Peruvian Andes Mountains store and supply freshwater to hundreds of thousands of people in central Peru. Atmospheric black carbon (BC) is known to accelerate melting of snow and ice, in addition to contributing to air pollution and the health of people. Currently there is limited understanding on the sources and temporal variability of BC in valley and mountain environments in Peru. To address this problem, this study combined surface observations of BC collected during 2022-2023 with WRF model simulations and HYSPLIT trajectories to analyze the dispersion and sources of BC in valley and high elevation environments and the associated local atmospheric circulations. Results show high BC concentrations are associated with the valley-mountain wind system that occurs on both sides of the Huaytapallana mountain range. A pronounced circulation occurs on the western slopes of Huaytapallana when concentrations of BC increase during daylight hours, which transports atmospheric pollutants from cities in the Mantaro River Valley to the Huaytapallana mountain range. Low concentrations of BC are associated with circulations from the east that are channeled by the pronounced ravines of the Andes-Amazon transition. On average, during the season of highest BC concentrations (July-November), the relative contributions of fossil fuels are dominant to biomass burning at the valley observatory and are slightly lower at the Huaytapallana observatory. These results demonstrate the need to promote mitigation actions to reduce emissions of BC and air pollution associated with forest fires and local anthropogenic activity.

Phenotypic Heterogeneity of Cancer Associated Fibroblasts in Cervical Cancer Progression: FAP as a Central Activation Marker.

Cervical cancer (CC) is the fourth leading cancer among women and is one of the principal gynecological malignancies. In the tumor microenvironment, cancer-associated fibroblasts (CAFs) play a crucial role during malignant progression, exhibiting a variety of heterogeneous phenotypes. CAFs express phenotypic markers like fibroblast activation protein (FAP), vimentin, S100A4, α-smooth muscle actin (αSMA), and functional markers such as MMP9. This study aimed to evaluate the protein expression of vimentin, S100A4, αSMA, FAP, and MMP9 in mesenchymal stem cells (MSC)-CAF cells, as well as in cervical cancer samples. MSC cells were stimulated with HeLa and SiHa tumor cell supernatants, followed by protein evaluation and cytokine profile to confirm differentiation towards a CAF phenotype. In addition, automated immunohistochemistry (IHQa) was performed to evaluate the expression of these proteins in CC samples at different stages. Our findings revealed a high expression of FAP in stimulated MSC cells, accompanied by the secretion of pro/anti-inflammatory cytokines. In the other hand, CC samples were observed to have high expression of FAP, vimentin, αSMA, and MMP9. Most importantly, there was a high expression of their activation proteins αSMA and FAP during the different stages. In the early stages, a myofibroblast-like phenotype (CAFs αSMA+ FAP+), and in the late stages a protumoral phenotype (CAF αSMA- FAP+). In summary, FAP has a crucial role in the activation of CAFs during cervical cancer progression.

Influence of biomass burning on ozone levels in the Megalopolis of Central Mexico during the COVID-19 lockdown.

The massive reductions in anthropogenic emissions resulting from the COVID-19 lockdown provided a unique opportunity to evaluate the effect of mitigation measures aiming to abate air pollution. In Mexico, the total lockdown period took place during the dry-hot season when biomass burning activity is enhanced. Here, we investigate the role of biomass burning emissions on regional ozone levels in the Megalopolis of Central Mexico. The studied period covers the lockdown phases 2 and 3, and the first month of the New Normal. We applied a factor separation technique and process analysis to estimate the pure and synergistic contributions of emission reductions under lockdown and that from biomass burning to daily ozone maximum concentrations in 7 metropolitan areas of different states in the Megalopolis. The results revealed that biomass burning plumes likely masked the effect of massive reductions from mobile emissions, impacted the PBL development during phase 3 and favored transition and mixed NOx-limited and VOC-limited regional regimes. This contributed to increased ozone production in the middle to lower PBL by changing the regional background levels which potentially could bias high ozone production efficiency estimations. Given the Megalopolis contribution to economic and societal development at national scale, our study suggests that ozone mitigation measures during the dry-hot season targeting mainly mobile emissions will likely be offset by biomass burning plumes. A regional and synergic policy aiming to control biomass burning would help to reduce the occurrence of high ozone levels in Central Mexico with the co-benefit of tackling short-lived climate pollutants.

Latitudinal and temporal distribution of aerosols and precipitable water vapor in the tropical Andes from AERONET, sounding, and MERRA-2 data.

The aerosol and precipitable water vapor (PW) distribution over the tropical Andes region is characterized using Aerosol Robotic Network (AERONET) observations at stations in Medellin (Colombia), Quito (Ecuador), Huancayo (Peru), and La Paz (Bolivia). AERONET aerosol optical depth (AOD) is interpreted using PM2.5 data when available. Columnar water vapor derived from ozone soundings at Quito is used to compare against AERONET PW. MERRA-2 data are used to complement analyses. Urban pollution and biomass burning smoke (BBS) dominate the regional aerosol composition. AOD and PM2.5 yearly cycles for coincident measurements correlate linearly at Medellin and Quito. The Andes cordillera's orientation and elevation funnel or block BBS transport into valleys or highlands during the two fire seasons that systematically impact South America. The February-March season north of Colombia and the Colombian-Venezuelan border directly impacts Medellin. Possibly, the March aerosol signal over Quito has a long-range transport component. At Huancayo and La Paz, AOD increases in September due to the influence of BBS in the Amazon. AERONET PW and sounding data correlate linearly but a dry bias with respect to soundings was identified in AERONET. PW and rainfall progressively decrease from north to south due to increasing altitude. This regional diagnosis is an underlying basis to evaluate future changes in aerosol and PW given prevailing conditions of rapidly changing atmospheric composition.

Influence of dengue virus serotypes on the abundance of Aedes aegypti insect-specific viruses (ISVs).

A comprehensive understanding of the virome in mosquito vectors is crucial for assessing the potential transmission of viral agents, designing effective vector control strategies, and advancing our knowledge of insect-specific viruses (ISVs). In this study, we utilized Oxford Nanopore Technologies metagenomics to characterize the virome of Aedes aegypti mosquitoes collected in various regions of Colombia, a country hyperendemic for dengue virus (DENV). Analyses were conducted on groups of insects with previous natural DENV infection (DENV-1 and DENV-2 serotypes), as well as mosquito samples that tested negative for virus infection (DENV-negative). Our findings indicate that the Ae. aegypti virome exhibits a similar viral composition at the ISV family and species levels in both DENV-positive and DENV-negative samples across all study sites. However, differences were observed in the relative abundance of viral families such as Phenuiviridae, Partitiviridae, Flaviviridae, Rhabdoviridae, Picornaviridae, Bromoviridae, and Virgaviridae, depending on the serotype of DENV-1 and DENV-2. In addition, ISVs are frequently found in the core virome of Ae. aegypti, such as Phasi Charoen-like phasivirus (PCLV), which was the most prevalent and showed variable abundance in relation to the presence of specific DENV serotypes. Phylogenetic analyses of the L, M, and S segments of the PCLV genome are associated with sequences from different regions of the world but show close clustering with sequences from Brazil and Guadeloupe, indicating a shared evolutionary relationship. The profiling of the Ae. aegypti virome in Colombia presented here improves our understanding of viral diversity within mosquito vectors and provides information that opens the way to possible connections between ISVs and arboviruses. Future studies aimed at deepening our understanding of the mechanisms underlying the interactions between ISVs and DENV serotypes in Ae. aegypti could provide valuable information for the design of effective vector-borne viral disease control and prevention strategies.IMPORTANCEIn this study, we employed a metagenomic approach to characterize the virome of Aedes aegypti mosquitoes, with and without natural DENV infection, in several regions of Colombia. Our findings indicate that the mosquito virome is predominantly composed of insect-specific viruses (ISVs) and that infection with different DENV serotypes (DENV-1 and DENV-2) could lead to alterations in the relative abundance of viral families and species constituting the core virome in Aedes spp. The study also sheds light on the identification of the genome and evolutionary relationships of the Phasi Charoen-like phasivirus in Ae. aegypti in Colombia, a widespread ISV in areas with high DENV incidence.

HPV-Negative and HPV-Positive Oral Cancer Cells Stimulate the Polarization of Neutrophils towards Different Functional Phenotypes In Vitro.

High-risk human papillomavirus (HPV) infection is one of the leading causes of oropharyngeal squamous cell carcinoma (OPSCC), while the correlation between HPV and oral squamous cell carcinoma (OSCC) remains controversial. The inflammatory infiltrate involved in these epithelial neoplasms differs based on their association with HPV. HPV- tumors show higher tumor-associated neutrophil (TAN) infiltration. It is believed that TANs can play a dual role in cancer by exerting either anti-tumorigenic or pro-tumorigenic effects. However, the impact of HPV status on neutrophil polarization remains unknown. Therefore, this study aimed to investigate the effect of OSCC cells, both HPV- and HPV16+, on the functional phenotype of neutrophils. Peripheral blood neutrophils were stimulated with supernatants from OSCC cell lines and non-tumorigenic HaCaT keratinocytes transduced with HPV16 E6/E7 oncogenes. Subsequently, cytokine production, cell viability, metabolism, expression of degranulation markers, and PD-L1 expression were evaluated. Our findings demonstrate that in contrast to UPCI:SCC154 (HPV+ OSCC) cells, the SCC-9 (HPV- OSCC) cell line induced a highly activated functional state in neutrophils, which is potentially associated with a pro-tumorigenic effect. The HaCaT 16-E7 supernatant only stimulated the activation of some neutrophil functions. Understanding the complex interplay between neutrophils and their microenvironment has the potential to identify TANs as viable therapeutic targets.

The Value of CXCL1, CXCL2, CXCL3, and CXCL8 as Potential Prognosis Markers in Cervical Cancer: Evidence of E6/E7 from HPV16 and 18 in Chemokines Regulation.

Cervical cancer (CC) is a serious global health issue, and it is well-known that HPV infection is the main etiological factor that triggers carcinogenesis. In cancer, chemokine ligands and receptors are involved in tumor cell growth, metastasis, leukocyte infiltration, and angiogenesis; however, information on the role played by E6/E7 of HPV16/18 in the modulation of chemokines is very limited. Therefore, this study aimed to determine whether chemokines are differentially expressed in CC-derived cell lines; if E6/E7 oncoproteins from HPV16 and 18 are capable of mediating chemokine expression, what is the expression profile of chemokines in tissues derived from CC and what is their impact on the overall survival of patients with this pathology? For this purpose, RNA sequencing and real-time PCR were performed on SiHa, HeLa, and C33A tumorigenic cell lines, on the non-tumorigenic HaCaT cells, and the E6/E7 HPV-transduced HaCaT cell models. Furthermore, chemokine expression and survival analysis were executed on 304 CC and 22 normal tissue samples from The Cancer Genome Atlas (TCGA) repository. The results demonstrate that CXCL1, CXCL2, CXCL3, and CXCL8 are regulated by E6/E7 of HPV16 and 18, are overexpressed in CC biopsies, and that their higher expression is related to a worse prognostic survival.

Gender heterophily and equality: a contribution to gender equality in the Chilean scientific sector.

Women's insertion or consolidation in science has been thoroughly researched. Such discussion could be particularly relevant concerning sustainable development goal five (SDG 5) on Gender Equality advancement. However, the debate is focused on women percentages inserted into scientific labor, leaving the issue of symbolic experience for women in research unaddressed and with little empirical support. The data come from a survey developed under a FONDECYT project, which studied knowledge production in Chile. Researchers obtained contacts through invitations on social networks such as Twitter, Facebook, and LinkedIn and databases containing scientists' emails working in Chile. The non-probabilistic sample collected 583 cases, with participants residing in 15 of the 16 country regions. As a result, this document presents the findings of a study on symbolic experience using an instrument to determine whether there are any homophily patterns. It aims to determine if scientists tend to cite others as referents only when they encounter a situation like their own. The findings reveal a clear way scientists estimate the effect of others in terms of their gender homophily. This intervening factor could be crucial in reproducing the disparities and asymmetries that characterize Chile's scientific field.

Effect of Proximal Row Carpectomy and Wrist Arthrodesis on the Resting Length of Extrinsic Digit Flexor Tendons: A Cadaveric Study.

Background Spastic joint contractures remain a complex and challenging condition. For patients with upper extremity spastic dysfunction, improving the muscle balance is essential to maximize their hand function. Multiple procedures, including proximal row carpectomy (PRC) and wrist arthrodesis (WA), are considered among the different surgical alternatives. However, the biomechanical consequences of these two procedures have not been well described in current literature. Hence, the objective of our study is to assess the change in the extrinsic digit flexor tendon resting length after proximal row carpectomy and wrist arthrodesis. Methods Six fresh-frozen cadaver upper extremities (four females and two males) with no obvious deformity underwent dissection, PRC, and WA. All the flexor digitorum profundus (FDP), flexor digitorum superficialis (FDS), and flexor pollicis longus (FPL) tendons were marked proximally 1-cm distal to their respective myotendinous junction and cut distally at the marked point. The overlapping segment of each distal flexor tendon from its proximal mark was considered the amount of flexor tendon resting length change after PRC and WA. A descriptive evaluation was performed to assess the increment in tendon resting length. Additionally, a regression analysis was performed to evaluate the relation between the tendon resting length and the proximal carpal row height. Results Following PRC and WA, the mean digit flexor tendon resting length increment achieved across all tendons was 1.88 cm (standard deviation [SD] = 0.45; range: 1.00-3.00 cm). A weak direct relationship ( R = 0.0334) between the increment in tendon resting length and proximal carpal row height was initially suggested, although no statistical significance was demonstrated ( p = 0.811). Conclusion This study provides an anatomic description of the increased extrinsic digit flexor tendon resting length after PRC and WA in cadaveric specimens. Findings provide a useful framework to estimate the amount of extrinsic digit flexor resting length increment achieved after wrist fusion and the proximal carpal row removal.

Pan American League of Associations for Rheumatology Guidelines for the Treatment of Takayasu Arteritis.

OBJECTIVE: To develop the first evidence-based Pan American League of Associations for Rheumatology (PANLAR) guidelines for the treatment of Takayasu arteritis (TAK). METHODS: A panel of vasculitis experts developed a series of clinically meaningful questions addressing the treatment of TAK patients in the PICO (population/intervention/comparator/outcome) format. A systematic literature review was performed by a team of methodologists. The evidence quality was assessed according to the GRADE (Grading of Recommendations/Assessment/Development/Evaluation) methodology. The panel of vasculitis experts voted each PICO question and made recommendations, which required ≥70% agreement among the voting members. RESULTS: Eleven recommendations were developed. Oral glucocorticoids are conditionally recommended for newly diagnosed and relapsing TAK patients. The addition of nontargeted synthetic immunosuppressants (e.g., methotrexate, leflunomide, azathioprine, or mycophenolate mofetil) is recommended for patients with newly diagnosed or relapsing disease that is not organ- or life-threatening. For organ- or life-threatening disease, we conditionally recommend tumor necrosis factor inhibitors (e.g., infliximab or adalimumab) or tocilizumab with consideration for short courses of cyclophosphamide as an alternative in case of restricted access to biologics. For patients relapsing despite nontargeted synthetic immunosuppressants, we conditionally recommend to switch from one nontargeted synthetic immunosuppressant to another or to add tumor necrosis factor inhibitors or tocilizumab. We conditionally recommend low-dose aspirin for patients with involvement of cranial or coronary arteries to prevent ischemic complications. We strongly recommend performing surgical vascular interventions during periods of remission whenever possible. CONCLUSION: The first PANLAR treatment guidelines for TAK provide evidence-based guidance for the treatment of TAK patients in Latin American countries.

Pentoxifylline Inhibits TNF-α/TGF-ß1-Induced Epithelial-Mesenchymal Transition via Suppressing the NF-κB Pathway and SERPINE1 Expression in CaSki Cells.

Cervical cancer (CC) is one of the most common and deadly types of female cancer worldwide. Late diagnosis in CC increases the risk of tumor cells spreading to distant organs (metastasis). The epithelial-mesenchymal transition (EMT) is a fundamental process of cancer metastasis. Inflammation can lead to tumor progression, EMT induction, and metastasis. The inflammatory microenvironment is a potent inducer of EMT; inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α) and Transforming growth factor-beta (TGF-ß1) activate transcriptional factors such as STAT3, Snail, Smad, and the Nuclear Factor kappa light-chain-enhancer of activated beta cells (NF-κΒ), which drive EMT. Anti-inflammatory compounds may be an option in the disruption of EMT. PenToXifylline (PTX) possesses potent anti-inflammatory effects by inhibiting NF-κB activity. In addition, PTX exerts an anti-fibrotic effect by decreasing Smad2/3/4. We hypothesize that PTX could exert anti-EMT effects. CaSki human cervical tumor cells were exposed to TNF-α 10 ng/mL and TGF-ß1 alone or in combination for 5 days. Our results revealed that TNF-α and TGF-ß1 induced N-cadherin and Vimentin, confirming the induction of EMT. Furthermore, the combination of cytokines synergized the expression of mesenchymal proteins, enhanced IκBα and p65 phosphorylation, and upregulated Serpin family E member 1 (SERPINE1) mRNA. PTX pretreatment prior to the addition of TNF-α and TGF-ß1 significantly reduced N-cadherin and Vimentin levels. To our knowledge, this is the first time that this effect of PTX has been reported. Additionally, PTX reduced the phosphorylation of IκB-α and p65 and significantly decreased SERPINE1 expression, cell proliferation, migration, and invasion. In conclusion, PTX may counteract EMT in cervical cancer cells by decreasing the NF-κB and SERPINE1.

Could an event of extreme drought (2019-2020) affect the feeding ecology of Bubo magellanicus (Gmelin 1788) (Strigiformes: Strigidae) in a Mediterranean region of Chile?

Global warming generates changes in environmental conditions, affecting the spatial-temporal dynamics of precipitation and temperature. Droughts, events of low rainfall, are becoming more frequent and severe. In central Chile, from 2010 to date, an unprecedented drought event has developed, affecting the ecosystem and creating pressure on the dynamics of food webs. The present study analysed the trophic ecology of Bubo magellanicus, a top predator in the Mediterranean region of Chile, between 2019 and 2020 a period with a rainfall deficit of 72.6%. Our results established a diet mainly described by invertebrates (97.75%), in particular by the Gramnostola rosea spider (87.86%), and a low contribution of small vertebrates (2.24%). The trophic niche breadth (B = 0.37) and the standardised Levin's index (BSTA = 0.01) are the lowest recorded in the species B. magellanicus. A comparative analysis of trophic ecology with other studies developed in the same region established significant differences in the composition of the diet (frequency of occurrence of prey unit). This work provides evidence that droughts and other extreme environmental scenarios restructure the food webs of an ecosystem, with direct consequences on the trophic niche of the species, specifically top predators.

Splicing Characterization and Isoform Switch Events in Human Keratinocytes Carrying Oncogenes from High-Risk HPV-16 and Low-Risk HPV-84.

Infection of epithelial cells with high-risk HPV (HR-HPV) types, followed by expression of virus oncogenic proteins (E5, E6, and E7), leads to genomic imbalance, suppression of tumor inhibitors, and induction of oncogenes. Low-risk HPV (LR-HPV) may slow the rate at which cervical cancer spreads to an invasive stage since co-infection with LR-HPV is linked to a decreased risk of future invasive cancer than infection with HR-HPV alone. We then propose that cancer-progressing changes may be distinguished through identifying the functional differences between LR-HPV and HR-HPV. Lentiviral strategies were followed to establish HaCaT cells with constitutive expression of HPV oncogenes. RNAseq experiments were designed to analyze the transcriptome modulations caused by each of the E5, E6, and E7 oncogenes of HPV-16 and HPV-84 in HaCaT cells. We identified enhanced RNA degradation, spliceosome, and RNA polymerase pathways related to mRNA processing. ATTS (alternative transcription termination site) was discovered to be more prevalent in cells with HPV-16E5 than HPV-84E5. In HPV-16E6-infected cells, ATTS gain was significantly higher than ATTS loss. Cells with HPV-16E7 had more isoforms with intron retention (IR) than those with HPV-84E7. We identified switches in ADAM10, CLSPN, and RNPS1 that led to greater expression of the coding isoforms in HR-HPV. The results of this work highlight differences between LR-HPV and HR-HPV in mRNA processing. Moreover, crucial cervical cancer-related switch events were detected.

Magnetic resonance imaging findings of spontaneous pyomyoma in a premenopausal woman managed with myomectomy: A case report.

BACKGROUND: Acute fibroid complications are rare. However, failure to recognize and treat acute complications expeditiously when they occur can lead to catastrophic, even deadly, complications. Pyomyoma is a rare but potentially fatal condition resulting from infarction and infection of a fibroid through bacterial seeding and direct, hematogenous, or lymphatic dissemination. Even though the diagnosis is established through clinical and laboratory findings, imaging is an important complementary method to support the suspected diagnosis. CASE SUMMARY: Herein, we report a case of a pyomyoma in a nulliparous woman previously diagnosed with uterine leiomyomatosis according to ultrasound findings. The patient had previously attended the emergency room due to hypogastric pain unresponsive to analgesics. After a week of persistent pain, she developed sepsis without any identifiable foci. Magnetic resonance imaging revealed findings compatible with uterine myomatosis with red degeneration, and a possible diagnosis of a pyomyoma was made according to the imaging findings along with the patient's clinical features. We decided to perform myomectomy (which is an infrequently performed surgical treatment due to the procedure's intrinsic implications) due to the patient's desire to preserve fertility. Histopathologic results revealed a uterine leiomyoma with coagulative and liquefactive necrosis, while the tissue culture showed gram-negative cocci bacteria, which were successfully treated using antibiotic therapy. The patient's health status improved after several days. CONCLUSION: The main diagnostic tools to evaluate pyomyomas are the clinical and laboratory findings as well as tissue cultures. Nonetheless, magnetic resonance imaging can help to corroborate these findings as well as to better characterize myomas with its different complications.

New Insights into rice pyrimidine catabolic enzymes.

Introduction: Rice is a primary global food source, and its production is affected by abiotic stress, caused by climate change and other factors. Recently, the pyrimidine reductive catabolic pathway, catalyzed by dihydropyrimidine dehydrogenase (DHPD), dihydropyrimidinase (DHP) and ß-ureidopropionase (ß-UP), has emerged as a potential participant in the abiotic stress response of rice. Methods: The rice enzymes were produced as recombinant proteins, and two were kinetically characterized. Rice dihydroorotate dehydrogenase (DHODH), an enzyme of pyrimidine biosynthesis often confused with DHPD, was also characterized. Salt-sensitive and salt-resistant rice seedlings were subjected to salt stress (24 h) and metabolites in leaves were determined by mass spectrometry. Results: The OsDHPD sequence was homologous to the C-terminal half of mammalian DHPD, conserving FMN and uracil binding sites, but lacked sites for Fe/S clusters, FAD, and NADPH. OsDHPD, truncated to eliminate the chloroplast targeting peptide, was soluble, but inactive. Database searches for polypeptides homologous to the N-terminal half of mammalian DHPD, that could act as co-reductants, were unsuccessful. OsDHODH exhibited kinetic parameters similar to those of other plant DHODHs. OsDHP, truncated to remove a signal sequence, exhibited a kcat/Km = 3.6 x 103 s-1M-1. Osb-UP exhibited a kcat/Km = 1.8 x 104 s-1M-1. Short-term salt exposure caused insignificant differences in the levels of the ureide intermediates dihydrouracil and ureidopropionate in leaves of salt-sensitive and salt-resistant plants. Allantoin, a ureide metabolite of purine catabolism, was found to be significantly higher in the resistant cultivar compared to one of the sensitive cultivars. Discussion: OsDHP, the first plant enzyme to be characterized, showed low kinetic efficiency, but its activity may have been affected by truncation. Osb-UP exhibited kinetic parameters in the range of enzymes of secondary metabolism. Levels of two pathway metabolites were similar in sensitive and resistant cultivars and appeared to be unaffected by short-term salt exposure."

FOXP3 Isoforms Expression in Cervical Cancer: Evidence about the Cancer-Related Properties of FOXP3Δ2Δ7 in Keratinocytes.

Cervical cancer (CC) is the fourth most common type of cancer among women; the main predisposing factor is persistent infection by high-risk human papillomavirus (hr-HPV), mainly the 16 or 18 genotypes. Both hr-HPVs are known to manipulate the cellular machinery and the immune system to favor cell transformation. FOXP3, a critical transcription factor involved in the biology of regulatory T cells, has been detected as highly expressed in the tumor cells of CC patients. However, its biological role in CC, particularly in the keratinocytes, remained unclarified. Therefore, this work aimed to uncover the effect of FOXP3 on the biology of the tumoral cells. First, public databases were analyzed to identify the FOXP3 expression levels and the transcribed isoforms in CC and normal tissue samples. The study's findings demonstrated an increased expression of FOXP3 in HPV16+ CC samples. Additionally, the FOXP3Δ2 variant was detected as the most frequent splicing isoform in tumoral cells, with a high differential expression level in metastatic samples. However, the analysis of FOXP3 expression in different CC cell lines, HPV+ and HPV-, suggests no relationship between the presence of HPV and FOXP3 expression. Since the variant FOXP3Δ2Δ7 was found highly expressed in the HPV16+ SiHa cell line, a model with constitutive expression of FOXP3Δ2Δ7 was established to evaluate its role in proliferation, migration, and cell division. Finally, RNAseq was performed to identify differentially expressed genes and enriched pathways modulated by FOXP3Δ2Δ7. The exogenous expression of FOXP3Δ2Δ7 promotes cell division, proliferation, and migration. The transcriptomic analyses highlight the upregulation of multiple genes with protumor activities. Moreover, immunological and oncogenic pathways were detected as highly enriched. These data support the hypothesis that FOXP3Δ2Δ7 in epithelial cells induces cancer-related hallmarks and provides information about the molecular events triggered by this isoform, which could be important for developing CC.

On the Regulation of NF-κB Pathway by HPV Oncoproteins: Are Pathway Inhibitors a Good Alternative for the Treatment of Cervical Cancer?

Cervical cancer (CC) is one of the most prevalent cancer-related pathologies in the female population. It is considered the second leading cause of cancer-related deaths in developing countries. The most important etiological factor for the development of CC is the persistent infection with high-risk human papillomavirus. HPV-oncoproteins have evolved to modulate cellular mechanisms to permit viral replication and the generation of new infectious viral particles. When the viral infection persists, there is an uncontrolled viral protein expression essential to commence and maintain the transformation of infected cells. Different cell pathways are affected during the transformation stage, including the NF-κB signaling pathway. NF-κB controls different cellular mechanisms, and its role is critical for various processes, such as immunity, inflammation, cell differentiation, growth, and survival. NF-κB plays a double role in the development of CC. Evidence suggests that in the early stages of viral infection, the NF-κB activity impairs viral transcription and is beneficial for avoiding cellular immortalization. However, in the advanced stages of cervical carcinogenesis, the activation of the NF-κB correlates with a poor prognosis. Here, we discuss some aspects of NF-κB activity during the development of CC and the use of NF-κB inhibitors to treat this pathology.