Radiopaque and Biocompatible PMMA Bone Cement Triggered by Nano Tantalum Carbide and Its Osteogenic Performance.

Poly(methyl methacrylate) (PMMA) bone cements have been widely used in orthopedics; thanks to their excellent mechanical properties, biocompatibility, and chemical stability. Barium sulfate and zirconia are usually added into PMMA bone cement to enhance the X-ray radiopacity, while the mechanical strength, radiopacity, and biocompatibility are not well improved. In this study, an insoluble and corrosion-resistant ceramic, tantalum carbide (TaC), was added into the PMMA bone cement as radiopacifies, significantly improving the mechanical, radiopaque, biocompatibility, and osteogenic performance of bone cement. The TaC-PMMA bone cement with varied TaC contents exhibits compressive strength over 100 MPa, higher than that of the commercial 30% BaSO4-PMMA bone cement. Intriguingly, when the TaC content reaches 20%, the radiopacity is equivalent to the commercial bone cement with 30% of BaSO4 in PMMA. The cytotoxicity and osteogenic performance indicate that the incorporation of TaC not only enhances the osteogenic properties of PMMA but also does not reduce cell viability. This study suggests that TaC could be a superior and multifunctional radio-pacifier for PMMA bone cement, offering a promising avenue for improving patient outcomes in orthopedic applications.

Prevalence of tooth agenesis and supernumerary teeth related to different Thai cleft lip and cleft palate populations.

BACKGROUND: Pattern of dental anomalies encountered in cleft patients shows subtle signs of genetic involvement. This study aimed to evaluate the prevalence and pattern of tooth agenesis and supernumerary teeth in Thai cleft population according to the cleft type. METHODS: Data collected from patients with cleft lip and palate, who had been treated at Tawanchai Cleft Center, Khon Kaen University, Thailand, available during year 2012-2022, were investigated. Records from 194 patients with non-syndromic clefts met the inclusion criteria. Standard dental records, and at least either orthopantomogram (OPG) or cone beam computed tomography (CBCT), were examined. Statistical analysis was performed using chi-square and binominal test (p ≤ 0.05). RESULTS: Prevalence of tooth agenesis was higher (77.3%) than that of supernumerary teeth (5.7%) and was more common in bilateral cleft lip and palate (BCLP) (88.1%) than in unilateral cleft lip and palate (UCLP) (72.6%) (p = 0.017). The upper lateral incisor was more frequently affected (46.4%), followed by the upper second premolar. The number of missing teeth observed on the left side was significantly higher. Patients with left UCLP (ULCLP) had the highest prevalence of tooth agenesis. A total of 41 tooth agenesis code (TAC) patterns was found. The prevalence of supernumerary teeth was comparable with 6.6% of ULCLP, 5.1% of BCLP, and 4.5% of URCLP. Tooth-number anomalies were observed more often in the BCLP and were most likely to occur on the left side of the maxilla. Both types of anomalies could be featured in a small proportion of cleft patients. CONCLUSIONS: More than half of the patients with non-syndromic cleft lip and palate in this study, presented with tooth-number anomalies. Tooth agenesis was approximately 10-time more prevalent than supernumerary teeth. Tooth agenesis was likely to appear on the left-side of the maxilla regardless of the laterality of the cleft.

Evaluating a novel vertical traction device for early closure in open abdomen management: a consecutive case series.

Background: In emergency surgery, managing abdominal sepsis and critically ill patients with imminent abdominal compartment syndrome (ACS) using an open abdomen (OA) approach has become standard practice for damage control. To prevent significant complications associated with OA therapy, such as abdominal infections, entero-atmospheric fistula (EAF), and abdominal wall hernia formation, early definitive fascial closure (DFC) is crucial. This study aims to assess the feasibility of a novel device designed to facilitate early fascial closure in patients with an open abdomen. Methods: Between 2019 and 2020, nine patients undergoing open abdomen management were enrolled in this study. All patients were treated using vertical mesh-mediated fascial traction combined with a novel vertical traction device (VTD). Data from these cases were collected and retrospectively analyzed. Results: In this study, all patients were treated with OA due to impending ACS. Three patients died before achieving DFC, while the remaining six patients successfully underwent DFC. The mean number of surgical procedures after OA was 3 ± 1, and the mean time to DFC was 9 ± 3 days. The use of the VTD in combination with negative pressure wound therapy (NPWT) resulted in a 76% reduction in fascia-to-fascia distance until DFC was achieved. The application of the VTD did not affect ventilation parameters or the Simplified Acute Physiology Score II (SAPS II), but intra-abdominal pressure (IAP) was reduced from 31 ± 8 mmHg prior to OA to 8.5 ± 2 mmHg after applying the device. The primary complication associated with the device was skin irritation, with three patients developing skin blisters as the most severe manifestation. Conclusion: Overall, the novel VTD appears to be a safe and feasible option for managing OA cases. It may reduce complications associated with OA by promoting early definitive fascial closure.

Prevalence and dynamics of antimalarial drug resistance mutations among the Plasmodium falciparum isolates in TAK Province, Thailand, during the period of 1998-2001.

Despite the overall decline in malaria cases in Thailand, continuous surveillance in endemic areas remains crucial. This retrospective analysis examined Plasmodium falciparum samples from Tak province, Thailand, collected in 1998, 1999, and 2001, to investigate the prevalence and evolution of antimalarial genotypic drug resistance. The study revealed a high prevalence of drug-resistant P. falciparum, particularly to mefloquine and sulfadoxine/pyrimethamine, with significant mutations in genes associated with resistance. Notably, mutations indicative of artemisinin resistance, such as those in the kelch13 gene, were detected at low frequencies, suggesting an evolving resistance pattern. The underlying cause of these resistance mutations appears to be the historical and widespread use of these antimalarial drugs, which exerted selective pressure on the parasite population. These findings underscore the necessity of ongoing surveillance and adaptive control strategies to manage drug resistance, guide treatment policies, and prevent potential outbreaks, even as malaria cases decrease. Continuous monitoring and research are imperative to sustain malaria elimination efforts and address the dynamic challenges posed by evolving drug-resistant strains.

A modified glycosylase base editor without predictable DNA off-target effects.

Glycosylase base editor (GBE) can induce C-to-G transversion in mammalian cells, showing great promise for the treatment of human genetic disorders. However, the limited efficiency of transversion and the possibility of off-target effects caused by Cas9 restrict its potential clinical applications. In our recent study, we have successfully developed TaC9-CBE and TaC9-ABE by separating nCas9 and deaminase, which eliminates the Cas9-dependent DNA off-target effects without compromising editing efficiency. We developed a novel GBE called TaC9-GBEYE1, which utilizes the deaminase and UNG-nCas9 guided by TALE and sgRNA, respectively. TaC9-GBEYE1 showed comparable levels of on-target editing efficiency to traditional GBE at 19 target sites, without any off-target effects caused by Cas9 or TALE. The TaC9-GBEYE1 is a safe tool for gene therapy.

Associations between dietary total antioxidant capacity and sarcopenia: a cross-sectional study.

BACKGROUND: No study has investigated the relationship between dietary total antioxidant capacity and sarcopenia so far. OBJECTIVE: This study aimed to investigate the association between dietary Total Antioxidant Capacity (d-TAC) and sarcopenia in elderly adults. METHODS: In this cross-sectional study we enrolled 300 elderly people (150 men and 150 women) aged ≥ 55 years using cluster random sampling method. Sarcopenia was defined based on European Working Group on Sarcopenia (EWGSOP) definition. A DXA scanner, a squeeze bulb dynamometer and a 4-Meter walk gait speed test was used to measure Appendicular Skeletal Muscle (ASM), muscle strength and muscle performance respectively. We also used a Block-format 117-item food frequency questionnaire (FFQ) to assess dietary intakes of participants. Multivariable logistic regression models were applied to examine the association between d-TAC and sarcopenia. RESULTS: Mean ± SD age of study participants and their BMI was 66.8 ± 7.72 year and 27.3 ± 4.2 kg/m2, respectively. People in the highest tertile of d-TAC had the greatest hand grip strength (11.9 ± 3.63 vs. 10.4 ± 3.55 psi, p = 0.009) and had lower odds of sarcopenia compared with those in the lowest tertile, either before (OR = 0.39; 95% CI: 0.17, 0.88) or after adjustment for potential confounders (OR = 0.33; 95% CI: 0.11, 0.95). No other significant association was seen between d-TAC and components of sarcopenia. CONCLUSION: We found an inverse association between dietary total antioxidant capacity and odds of sarcopenia. No significant association was seen between d-TAC and individual components of sarcopenia. Further studies are needed to confirm our findings.

Empagliflozin rescues pro-arrhythmic and Ca2+ homeostatic effects of transverse aortic constriction in intact murine hearts.

We explored physiological effects of the sodium-glucose co-transporter-2 inhibitor empagliflozin on intact experimentally hypertrophic murine hearts following transverse aortic constriction (TAC). Postoperative drug (2-6 weeks) challenge resulted in reduced late Na+ currents, and increased phosphorylated (p-)CaMK-II and Nav1.5 but not total (t)-CaMK-II, and Na+/Ca2+ exchanger expression, confirming previous cardiomyocyte-level reports. It rescued TAC-induced reductions in echocardiographic ejection fraction and fractional shortening, and diastolic anterior and posterior wall thickening. Dual voltage- and Ca2+-optical mapping of Langendorff-perfused hearts demonstrated that empagliflozin rescued TAC-induced increases in action potential durations at 80% recovery (APD80), Ca2+ transient peak signals and durations at 80% recovery (CaTD80), times to peak Ca2+ (TTP100) and Ca2+ decay constants (Decay30-90) during regular 10-Hz stimulation, and Ca2+ transient alternans with shortening cycle length. Isoproterenol shortened APD80 in sham-operated and TAC-only hearts, shortening CaTD80 and Decay30-90 but sparing TTP100 and Ca2+ transient alternans in all groups. All groups showed similar APD80, and TAC-only hearts showed greater CaTD80, heterogeneities following isoproterenol challenge. Empagliflozin abolished or reduced ventricular tachycardia and premature ventricular contractions and associated re-entrant conduction patterns, in isoproterenol-challenged TAC-operated hearts following successive burst pacing episodes. Empagliflozin thus rescues TAC-induced ventricular hypertrophy and systolic functional, Ca2+ homeostatic, and pro-arrhythmogenic changes in intact hearts.

Engineering an enzyme-like catalytic sensor for on-site dual-mode evaluation of total antioxidant capacity.

A novel Fe-MoOx nanozyme, engineered with enhanced peroxidase (POD)-like activity through strategic doping and the creation of oxygen vacancies, is introduced to catalyze the oxidation of TMB with high efficiency. Furthermore, Fe-MoOx is responsive to single electron transfer (SET) and hydrogen atom transfer (HAT) mechanisms related to antioxidants and can serve as a desirable nanozyme for total antioxidant capacity (TAC) determination. The TAC colorimetric platform can reach a low LOD of 0.512 µM in solution and 24.316 µM in the smartphone-mediated RGB hydrogel (AA as the standard). As proof of concept, the practical application in real samples was explored. The work paves a promising avenue to design diverse nanozymes for visual on-site inspection of food quality.

Comparative Assessment of Total Antioxidant Capacity of Unstimulated Saliva Which Can Reflect the Oxidative Stress between Autism Children and Normal Children.

Aim: To assess the level of total antioxidant capacity (TAC) in the unstimulated saliva of autism children and normal children. Methods: A total of 60 children participated in the study (autism children-30; normal children-30) in the age-group of 7-14 years, at a Special Needs Children's Home in Salem district. Both groups were further subdivided into subgroups of 15 children each (caries-free and caries-active). All children were given instructions regarding saliva sample collection, and unstimulated saliva samples were collected in sterile cryovials and transported to the laboratory at 4°C, where the TAC of saliva was evaluated using the spectrophotometric assay. Results: TAC of autism children was comparable to that of normal children due to personal care and improved diet. TAC was increased in caries-active children when compared to caries-free children in both groups. When comparing the mean values of TAC in caries-active and caries-free children of both groups, it was not statistically significant. So, from the above results, it can be assumed that the diet, age, and caries activity have a definitive influence on the TAC level of saliva. Conclusion: Personal hygiene, diet, age, and caries activity have a definitive influence on the level of TAC in saliva.

Synthesis of Ag-Doped Tetrahedral Amorphous Carbon Coatings and Their Antibiofilm Efficacy for Medical Implant Application.

Tetrahedral amorphous carbon (taC) is a hydrogen-free carbon with extensive properties such as hardness, optical transparency, and chemical inertness. taC coatings have attracted much attention in recent times, as have coatings doped with a noble metal. A known antimicrobial metal agent, silver (Ag), has been used as a dopant in taC, with different Ag concentrations on the Ti64 coupons using a hybrid filtered cathodic vacuum arc (FCVA) and magnetron sputtering system. The physiochemical properties of the coated surface were investigated using spectroscopic and electron microscopy techniques. A doping effect of Ag-taC on biofilm formation was investigated and found to have a significant effect on the bacterial-biofilm-forming bacteria Staphylococcus aureus and Pseudomonas aeruginosa depending on the concentration of Ag. Further, the effect of coated and uncoated Ag-taC films on a pathogenic bacterium was examined using SEM. The result revealed that the Ag-taC coatings inhibited the biofilm formation of S. aureus. Therefore, this study demonstrated the possible use of Ag-taC coatings against biofilm-related complications on medical devices and infections from pathogenic bacteria.

The atypical antipsychotic aripiprazole alters the outcome of disseminated Candida albicans infections.

Invasive fungal infections impose an enormous clinical, social, and economic burden on humankind. One of the most common species responsible for invasive fungal infections is Candida albicans. More than 30% of patients with disseminated candidiasis fail therapy with existing antifungal drugs, including the widely used azole class. We previously identified a collection of 13 medications that antagonize the activity of the azoles on C. albicans. Although gain-of-function mutations responsible for antifungal resistance are often associated with reduced fitness and virulence, it is currently unknown how exposure to azole antagonistic drugs impacts C. albicans physiology, fitness, or virulence. In this study, we examined how exposure to seven azole antagonists affects C. albicans phenotype and capacity to cause disease. Most of the azole antagonists appear to have little impact on fungal growth, morphology, stress tolerance, or gene transcription. However, aripiprazole had a modest impact on C. albicans hyphal growth and increased cell wall chitin content. It also aggravated the disseminated C. albicans infections in mice. This effect was abrogated in immunosuppressed mice, indicating that it is at least in part dependent upon host immune responses. Collectively, these data provide proof of principle that unanticipated drug-fungus interactions have the potential to influence the incidence and outcomes of invasive fungal disease.

ERK3 is involved in regulating cardiac fibroblast function.

ERK3/MAPK6 activates MAP kinase-activated protein kinase (MK)-5 in selected cell types. Male MK5 haplodeficient mice show reduced hypertrophy and attenuated increase in Col1a1 mRNA in response to increased cardiac afterload. In addition, MK5 deficiency impairs cardiac fibroblast function. This study determined the effect of reduced ERK3 on cardiac hypertrophy following transverse aortic constriction (TAC) and fibroblast biology in male mice. Three weeks post-surgery, ERK3, but not ERK4 or p38α, co-immunoprecipitated with MK5 from both sham and TAC heart lysates. The increase in left ventricular mass and myocyte diameter was lower in TAC-ERK3+/- than TAC-ERK3+/+ hearts, whereas ERK3 haploinsufficiency did not alter systolic or diastolic function. Furthermore, the TAC-induced increase in Col1a1 mRNA abundance was diminished in ERK3+/- hearts. ERK3 immunoreactivity was detected in atrial and ventricular fibroblasts but not myocytes. In both quiescent fibroblasts and "activated" myofibroblasts isolated from adult mouse heart, siRNA-mediated knockdown of ERK3 reduced the TGF-ß-induced increase in Col1a1 mRNA. In addition, intracellular type 1 collagen immunoreactivity was reduced following ERK3 depletion in quiescent fibroblasts but not myofibroblasts. Finally, knocking down ERK3 impaired motility in both atrial and ventricular myofibroblasts. These results suggest that ERK3 plays an important role in multiple aspects of cardiac fibroblast biology.

The importance of oxidative biomarkers in diagnosis, treatment, and monitoring schizophrenia patients.

INTRODUCTION: The etiology of schizophrenia (SCZ), an incredibly complex disorder, remains multifaceted. Literature suggests the involvement of oxidative stress (OS) in the pathophysiology of SCZ. OBJECTIVES: Determination of selected OS markers and brain-derived neurotrophic factor (BDNF) in patients with chronic SCZ and those in states predisposing to SCZ-first episode psychosis (FP) and ultra-high risk (UHR). MATERIALS AND METHODS: Determination of OS markers and BDNF levels by spectrophotometric methods and ELISA in 150 individuals (116 patients diagnosed with SCZ or in a predisposed state, divided into four subgroups according to the type of disorder: deficit schizophrenia, non-deficit schizophrenia, FP, UHR). The control group included 34 healthy volunteers. RESULTS: Lower activities of analyzed antioxidant enzymes and GSH and TAC concentrations were found in all individuals in the study group compared to controls (p < 0.001). BDNF concentration was also lower in all groups compared to controls except in the UHR subgroup (p = 0.01). Correlations were observed between BDNF, R-GSSG, GST, GPx activity, and disease duration (p < 0.02). A small effect of smoking on selected OS markers was also noted (rho<0.06, p < 0.03). CONCLUSIONS: OS may play an important role in the pathophysiology of SCZ before developing the complete clinical pattern of the disorder. The redox imbalance manifests itself with such severity in individuals with SCZ and in a state predisposing to the development of this psychiatric disease that natural antioxidant systems become insufficient to compensate against it completely. The discussed OS biomarkers may support the SCZ diagnosis and predict its progression.

Association Between Dietary Intake After Roux-en-Y Gastric Bypass Surgery and Antioxidant/inflammatory Status: A 6-Month Pilot Prospective Cohort Study.

BACKGROUND/AIM: Adipose tissue can increase levels of inflammation and oxidative stress, which explains the relationship between obesity and many chronic diseases. Weight loss, changes in adipose tissue metabolism, and dietary nutrient intake changes following bariatric surgery could affect a number of oxidative- and inflammation-related factors. Therefore, this study aimed to assess the potential relationship between dietary intake and inflammatory/antioxidant markers in the 6 months following Roux-en-Y gastric bypass surgery (RYGB). MATERIAL AND METHODS: This pilot prospective cohort study included 45 patients with severe obesity who underwent RYGB. The patients were assessed at three different time points: baseline, 3 months, and 6 months post-surgery. Throughout the study, dietary intake data, levels of total antioxidant capacity (TAC), NF-κB, and serum levels of certain micronutrients were measured three times. Dietary macro- and micronutrient intake data were obtained three times throughout the study using the 24-h food recall questionnaire. RESULTS: The analysis of dietary indices in the present study found a significant positive correlation between the dietary intake of zinc, copper, MUFA, and serum TAC levels. It also revealed a significant inverse correlation between serum levels of NF-κB with vitamin E and PUFA intake. Additionally, there was a significant positive association between the amount of dietary carbohydrates and saturated fatty acids intake and the levels of NF-κB. Furthermore, within 3 to 6 months after the surgery, patients experienced an increase in serum levels of TAC, ferritin, vitamin D3, vitamin B12, and folate. However, there was a decrease in serum levels of NF-κB, zinc, and copper. CONCLUSIONS: Weight loss and nutritional status may potentially impact oxidative stress and inflammation levels within 6 months following RYGB surgery. Further research is necessary to comprehensively investigate the different facets of this correlation and elucidate the precise underlying mechanism.

The zinc cluster transcription factor Znc1 regulates Rta3-dependent miltefosine resistance in Candida albicans.

Zinc cluster transcription factors (ZCFs) are a family of transcription regulators that are almost exclusively found in the fungal kingdom. Activating mutations in the ZCFs Mrr1, Tac1, and Upc2 frequently cause acquired resistance to the widely used antifungal drug fluconazole in the pathogenic yeast Candida albicans. Similar to a hyperactive Tac1, a constitutively active form of the ZCF Znc1 causes increased fluconazole resistance by upregulating the multidrug efflux pump-encoding gene CDR1. Hyperactive forms of both Tac1 and Znc1 also cause overexpression of RTA3, which encodes a seven-transmembrane receptor protein involved in the regulation of asymmetric lipid distribution in the plasma membrane. RTA3 expression is also upregulated by miltefosine, an antiparasitic drug that is active against fungal pathogens and considered for treatment of invasive candidiasis, and rta3Δ mutants are hypersensitive to miltefosine. We found that activated forms of both Tac1 and Znc1 confer increased miltefosine resistance, which was dependent on RTA3 whereas CDR1 was dispensable. Intriguingly, the induction of RTA3 expression by miltefosine depended on Znc1, but not Tac1, in contrast to the known Tac1-dependent RTA3 upregulation by fluphenazine. In line with this observation, znc1Δ mutants were hypersensitive to miltefosine, whereas tac1Δ mutants showed wild-type tolerance. Forced expression of RTA3 reverted the hypersensitivity of znc1Δ mutants, demonstrating that the hypersensitivity was caused by the inability of the mutants to upregulate RTA3 in response to the drug. These findings establish Znc1 as a key regulator of miltefosine-induced RTA3 expression that is important for wild-type miltefosine tolerance. IMPORTANCE: Transcription factors are central regulators of gene expression, and knowledge about which transcription factor regulates specific genes in response to a certain signal is important to understand the behavior of organisms. In the pathogenic yeast Candida albicans, the RTA3 gene is required for wild-type tolerance of miltefosine, an antiparasitic drug that is considered for treatment of invasive candidiasis. Activated forms of the transcription factors Tac1 and Znc1 cause constitutive overexpression of RTA3 and thereby increased miltefosine resistance, but only Tac1 mediates upregulation of RTA3 in response to the known inducer fluphenazine. RTA3 expression is also induced by miltefosine, and we found that this response depends on Znc1, whereas Tac1 is dispensable. Consequently, znc1Δ mutants were hypersensitive to miltefosine, whereas tac1Δ mutants showed wild-type tolerance. These findings demonstrate that Znc1 is the key regulator of RTA3 expression in response to miltefosine that is important for wild-type miltefosine tolerance.

Thermodynamic, kinetic, and equilibrium studies of Cu(II), Cd(II), Ni(II), and Pb(II) ion biosorption onto treated Ageratum conyzoid biomass.

The issue of environmental contamination, particularly caused by the existence of heavy metal particles, is a major and widely recognized subject that receives substantial global attention. The remediation of Cu(II), Cd(II), Ni(II), and Pb(II) ionic metal particles from synthetic wastewater using chemically treated plant leaves of Ageratum conyzoides (TAC) as a biosorbent was investigated. The biosorption process was implemented utilizing a batch system, wherein several operational parameters were considered, including temperature, pH, agitation time, biosorbent dosage, and initial concentration of the metal ion. Langmuir, Freundlich, Temkin, and D-R isotherm models were used to evaluate equilibrium data. The analyzed parameter exhibits characteristics that were best fitted with the Langmuir isotherm. The observed biosorption capacities (qm) of Cu(II), Pb(II), Ni(II), and Cd(II) ions on the TAC were measured as 51.573, 30.49, 33.53, and 35.91 mg/g, respectively, at a temperature of 22 °C. The affinity sequence of these metal ions follows the order Cu(II) > Pb(II) > Ni(II) > Cd(II). The measured values for the biosorption free energy change (ΔG) of Cu(II), Pb(II), Cd(II), and Ni(II) metal ions ranged from -1.017 to -4.723, -1.368 to -3.612, -2.785 to -5.21, and -1.047 to -5.135 kJ/mol, respectively. The enthalpy (ΔH) for Cu(II), Pb(II), Cd(II), and Ni(II) were determined to be +19.33, +6.82, +14.83, and +38.07 kJ/mol, respectively. Similarly, the corresponding entropy changes (ΔS) for the same series of metal ions were recorded as +0.075, +0.064, +0.063, and +0.135 kJ/mol.K. The pseudo-second-order kinetic models yielded superior outcomes in comparison to the pseudo-first-order kinetic models. The findings of the experiment indicated that the TAC demonstrates favorable efficacy in extracting all four metal ions. Hence, the utilization of biomass derived from Ageratum conyzoides leaves has proven to be a viable and economically feasible approach for biosorption of all four metals.

Vitamins in Gynecologic Malignancies.

The combination of vitamin A and D derivatives with classical chemotherapeutic treatments results in more satisfactory outcomes. The use of drug combinations, such as 9cUAB130 with carboplatin and cisplatin with TAC-101, shows enhanced cytotoxic effects and reductions in ovarian tumor volume compared to single-drug treatments. Combining cisplatin with calcitriol and progesterone increases VDR expression, potentially enhancing the effectiveness of anticancer therapy in ovarian cancer. The effectiveness of vitamin derivatives in anticancer treatment may vary depending on the characteristics of the tumor and the cell line from which it originated. An increase in thiamine intake of one unit is associated with an 18% decrease in HPV infection. Higher intake of vitamin C by 50 mg/day is linked to a lower risk of cervical neoplasia. Beta-carotene, vitamin C, and vitamin E are associated with risk reductions of 12%, 15%, and 9% in endometrial cancer, respectively. A balanced daily intake of vitamins is important, as both deficiency and excess can influence cancer development. It has been observed that there is a U-shaped relationship between group B vitamins and metabolic markers and clinical outcomes.

Cardiomyocyte-specific RXFP1 overexpression protects against pressure overload-induced cardiac dysfunction independently of relaxin.

Heart failure (HF) prevalence is rising due to reduced early mortality and demographic change. Relaxin (RLN) mediates protective effects in the cardiovascular system through Relaxin-receptor 1 (RXFP1). Cardiac overexpression of RXFP1 with additional RLN supplementation attenuated HF in the pressure-overload transverse aortic constriction (TAC) model. Here, we hypothesized that robust transgenic RXFP1 overexpression in cardiomyocytes (CM) protects from TAC-induced HF even in the absence of RLN. Hence, transgenic mice with a CM-specific overexpression of human RXFP1 (hRXFP1tg) were generated. Receptor functionality was demonstrated by in vivo hemodynamics, where the administration of RLN induced positive inotropy strictly in hRXFP1tg. An increase in phospholamban-phosphorylation at serine 16 was identified as a molecular correlate. hRXFP1tg were protected from TAC without additional RLN administration, presenting not only less decline in systolic left ventricular (LV) function but also abrogated LV dilation and pulmonary congestion compared to WT mice. Molecularly, transgenic hearts exhibited not only a significantly attenuated fetal and fibrotic gene activation but also demonstrated less fibrotic tissue and CM hypertrophy in histological sections. These protective effects were evident in both sexes. Similar cardioprotective effects of hRXFP1tg were detectable in a RLN-knockout model, suggesting an alternative mechanism of receptor activation through intrinsic activity, alternative endogenous ligands or crosstalk with other receptors. In summary, CM-specific RXFP1 overexpression provides protection against TAC even in the absence of endogenous RLN. This suggests RXFP1 overexpression as a potential therapeutic approach for HF, offering baseline protection with optional RLN supplementation for specific activation.

The TAC1 Gene in Candida albicans: Structure, Function, and Role in Azole Resistance: A Mini-Review.

Candidiasis is a common fungal infection caused by Candida species, with Candida albicans being the most prevalent. Resistance to azole drugs, commonly used to treat Candida infections, poses a significant challenge. Transcriptional activator candidate 1 (TAC1) gene has emerged as a key player in regulating drug resistance in C. albicans. This review explores the structure and function of the TAC1 gene and its role in azole resistance. This gene encodes a transcription factor that controls the expression of genes involved in drug resistance, such as efflux pump genes (CDR1, CDR2, and MDR1) and ERG11. Mutations in TAC1 can increase these genes' expression and confer resistance to azoles. Various TAC1 gene mutations, mostly gain-of-function mutations, have been identified, which upregulate CDR1 and CDR2 expression, resulting in azole resistance. Understanding the mechanisms of azole resistance mediated by the TAC1 gene is crucial for the strategies in the effective antifungal development pipeline.

Comparison of DASH diet score and total antioxidant capacity of diet on serum levels of TMPRSS-2, inflammatory biomarkers, and disease severity in COVID-19 patients: A case-control study.

There is evidence that healthy diets improve the immune system and lessen the severity of infectious diseases such as COVID-19. We have investigated whether the dietary total antioxidant capacity (TAC) and dietary approach to stop hypertension (DASH) score could be associated with the occurrence and clinical outcomes of COVID-19. This case-control study included 120 adults who were admitted to the hospital. Dietary TAC and DASH diet scores were determined by a 138-item semi-quantitative food frequency questionnaire (FFQ). Inflammation-related markers including C-reactive protein (CRP) and transmembrane protease serine 2 (TMPRSS-2) differential were measured. Also, using chest radiology criteria, the severity of the disease was evaluated. The mean CRP values in the lowest and highest tertiles of either dietary TAC or DASH diet scores were 9.44 ± 11.26 and 3.52 ± 4.83 mg/dL (p = .003) or 9.04 ± 11.23 and 4.40 ± 6.23 mg/dL (p = .013), respectively. Individuals with higher dietary TAC were at a lower risk of COVID-19 (OR: 0.06, p < ·0001). Individuals with greater DASH diet scores were also at decreased odds of COVID-19 (OR: 0.12, p < ·0001). No significant associations were found between dietary TAC and DASH diet scores with severity of COVID-19 disease, CRP, or TMPRSS-2 (p > 0.05). The study found that adherence to a diet with higher dietary TAC and DASH diet scores may be protective against COVID-19 and improve outcomes of the disease. More research is needed to corroborate these findings.