Search Results (46)

A high-fat diet (HFD) has significant effects on health, leading to cardiovascular, metabolic, neurodegenerative, and psychiatric conditions and contributing to obesity and type 2 diabetes. Mitochondria, essential for energy production and oxidative metabolism, are adversely affected by a HFD, causing oxidative stress and impaired cellular function. Mutations in the OPA1 (OPtic Atrophy 1) gene, crucial for mitochondrial dynamics and functions, are responsible for dominant optic atrophy (DOA), a mitochondrial neurodegenerative disease associated with increased reactive oxygen species (ROS). The expressivity of DOA is highly variable, even within the same family. This suggests that both modifying genetics and environmental factors could influence the penetrance of the disease. We previously demonstrated that genetic background modulates DOA expressivity and now ask if this is also the case for external cues. We thus explore how OPA1 deficiency interacts with HFD-induced metabolic disturbances, hypothesizing that long-term HFD consumption impairs brain mitochondrial function and disrupts oxidative metabolism. OPA1^+/− mice were thus subjected to a HFD for a period of 12 weeks, and ROS levels and the expression of antioxidant genes were evaluated by Western blot and spectrophotometry. Cortices from high-fat diet-fed OPA1^+/− mice showed lower aconitase activity than those of their wild-type (WT) litter mates, indicative of an unbalanced increase in mitochondrial ROS. Accordingly, OPA1^+/− mice present lower levels of the antioxidant enzyme superoxide dismutase 2 compared to WT mice. Therefore, this study (i) reveals the onset of oxidative stress in brain cortices from OPA1^+/− mice challenged with a HFD, (ii) shows that diet is a modifying factor for DOA, and (iii) suggests that food control could be used to moderate the severity of the disease. Full article

Background: Patients with a HeartMate 3 (HM3) left ventricular assist device (LVAD) typically receive anticoagulation and antiplatelet therapy. The HM3 has shown a marked reduction in hemocompatibility-related adverse events (HRAEs) like stroke, bleeding, and pump thrombosis. This study evaluated whether aspirin (ASA) response influences HRAE incidence and if ASA sensitivity changes over time in HM3 recipients. Methods: This single-center, cross-sectional study included 32 HM3 patients (age: 59.0 ± 10.0 years, 15.6% female). ASA sensitivity was assessed twice using the VerifyNow assay, with ASA resistance defined by ASA reactivity units (ARU) > 550. The primary endpoint was HRAE incidence in ASA responders vs. non-responders over two consecutive follow-ups; the secondary endpoint was temporal changes in ASA resistance. Results: At the first follow-up, 13 (40.6%) patients were ASA-resistant, and 8 (28.6%) were resistant at the second follow-up, without significant change (p = 0.22). ASA non-responders and responders had similar ASA doses and baseline characteristics. No significant difference in HRAE incidence was found between ASA non-responders and responders (0.0% vs. 15.8%, p = 0.14), and no additional HRAEs occurred during follow-up. Conclusions: ASA resistance varied considerably among HM3 patients without significant temporal changes, and the demonstrated excellent hemocompatibility supports recent evidence that ASA may have a limited role in the antithrombotic regimen for HM3 recipients. Full article

As a reactive species, the red deer is sensitive to both negative exogenous and endogenous stimuli. An intensive hunting period may have a particularly negative impact on game animals. The aim of this study was to determine the plasma cortisol level and biochemical parameters in 25 wild red deer (Cervus elaphus) harvested during stalking hunts in correlation with the sex and age of the animals. The mean cortisol concentrations in the stags and hinds analyzed in this study were similar (20.2 and 21.5 ng/mL, respectively). Higher HDL cholesterol values were found in the blood of the hinds than in stags (p < 0.05). Similarly, the mean levels of LDL cholesterol, lactate dehydrogenase, and alanine aminotransferase were higher by 21%, 16%, and 42%, respectively, in the blood of the hinds. In contrast, the levels of alkaline phosphatase, bilirubin, and aspartate aminotransferase were higher in the stags (by 30%, 49%, and 36%, respectively). There was a negative correlation of the cortisol concentration with urea and bilirubin and a positive correlation between cortisol and aspartate aminotransferase in the stags (p < 0.05). In turn, a negative correlation was found between the cortisol and urea levels in the hinds (p < 0.05). In summary, the stress caused by stalking hunts and the characteristic behavior of red deer during the mating season had an impact on chosen biochemical parameters. The increased concentration of cortisol resulted in a decrease in the carcass mass, which may lead to the deterioration of the physical condition of animals on hunting grounds. Full article

The process of sexual reproduction in eukaryotes starts when gametes from two different sexes encounter each other. Paramecium, a unicellular eukaryote, undergoes conjugation and uses a gametic nucleus to enter the sexual reproductive process. The molecules responsible for recognizing mating partners, hypothetically called mating-type substances, are still unclear. We have identified an O³-type mating substance polypeptide and its gene sequence using protein chemistry, molecular genetics, immunofluorescence, RNA interference, and microinjection. The O³-type substance is a polypeptide found in the ciliary membranes, located from the head to the ventral side of cells. The O³-type substance has a kinase-like domain in its N-terminal part located outside the cell and four EF-hand motifs that bind calcium ions in its C-terminal part located inside the cell. RNA interference and immunofluorescence revealed that this polypeptide positively correlated with the expression of mating reactivity. Microinjection of an expression vector incorporating the O³Pc-MSP gene (Oms3) induced additional O³ mating type in the recipient clones of different mating types or syngen. Phylogenetic analysis indicates that this gene is widely present in eukaryotes and exhibits high homology among closely related species. The O³Pc-MSP (Oms3) gene had nine silent mutations compared to the complementary mating type of the E³ homologue gene. Full article

Colorectal cancer is the most common cancer that affects both sexes and has a poor prognosis due to aggressiveness and chemoresistance. Essential oils isolated from Calocedrus formosana (CF-EOs) have been shown to demonstrate anti-termite, antifungal, anti-mosquito, and anti-microbial activities. However, the anticancer effects of CF-EOs are not yet fully understood. Therefore, the present study aimed to explore the molecular mechanism underlying CF-EOs-mediated anti-proliferative activity in colon cancer cells. Here, cell impedance measurements showed that CF-EOs inhibit proliferation in colon cancer cells with wild-type or mutant p53. Flow cytometry revealed that CF-EOs at 20, 50 µg/mL significantly induced ROS generation and autophagy in both HCT116 p53-wt and HCT116 p53-null cell lines, whereas pretreatment with the ROS scavenger N-acetyl cysteine (NAC) markedly attenuated these changes. CF-EOs also induced apoptosis at 50 µg/mL in both lines, as determined by flow cytometry. Protein analysis showed that CF-EOs markedly induced apoptosis markers, including Trail, cleaved caspase-3, cleaved caspase-9, and cleaved PARP, as well as autophagy markers, such as the levels of ULK1, Atg5, Atg6, Atg7, and the conversion of LC3-I to LC3-II. CF-EOs were further found to inhibit the activity and expression of the NAD⁺-dependent deacetylase SIRT1 to increase the levels of acetylated p53 (Ac-p53) in p53-wt cells and acetylated c-Myc (Ac-c-Myc) in p53-null cells, ultimately inducing apoptosis in both lines. Interestingly, suppression of SIRT1 by CF-EOs enhanced the acetylation of ULK1, which in turn prompted ROS-dependent autophagy in colon cancer cells. The induction of apoptosis and autophagy by CF-EOs suggests that they may have potential as a promising new approach for treating cancer. Collectively, our results suggest that essential oils isolated from Calocedrus formosana act as a promising anticancer agent against colon cancer cells by targeting SIRT1 to induce ROS-mediated autophagy and apoptosis. Full article

‘Inner mitochondrial membrane peptidase 2 like’ (IMMP2L) is a nuclear-encoded mitochondrial peptidase that has been conserved through evolutionary history, as has its target enzyme, ‘mitochondrial glycerol phosphate dehydrogenase 2′ (GPD2). IMMP2L is known to cleave the mitochondrial transit peptide from GPD2 and another nuclear-encoded mitochondrial respiratory-related protein, cytochrome C1 (CYC1). However, it is not known whether IMMP2L peptidase activates or alters the activity or respiratory-related functions of GPD2 or CYC1. Previous investigations found compelling evidence of behavioural change in the Immp2l^KD−/− KO mouse, and in this study, EchoMRI analysis found that the organs of the Immp2l^KD−/− KO mouse were smaller and that the KO mouse had significantly less lean mass and overall body weight compared with wildtype littermates (p < 0.05). Moreover, all organs analysed from the Immp2l^KD−/− KO had lower relative levels of mitochondrial reactive oxygen species (mitoROS). The kidneys of the Immp2l^KD−/− KO mouse displayed the greatest decrease in mitoROS levels that were over 50% less compared with wildtype litter mates. Mitochondrial respiration was also lowest in the kidney of the Immp2l^KD−/− KO mouse compared with other tissues when using succinate as the respiratory substrate, whereas respiration was similar to the wildtype when glutamate was used as the substrate. When glycerol-3-phosphate (G3P) was used as the substrate for Gpd2, we observed ~20% and ~7% respective decreases in respiration in female and male Immp2l^KD−/− KO mice over time. Together, these findings indicate that the respiratory-related functions of mGpd2 and Cyc1 have been compromised to different degrees in different tissues and genders of the Immp2l^KD−/− KO mouse. Structural analyses using AlphaFold2-Multimer further predicted that the interaction between Cyc1 and mitochondrial-encoded cytochrome b (Cyb) in Complex III had been altered, as had the homodimeric structure of the mGpd2 enzyme within the inner mitochondrial membrane of the Immp2l^KD−/− KO mouse. mGpd2 functions as an integral component of the glycerol phosphate shuttle (GPS), which positively regulates both mitochondrial respiration and glycolysis. Interestingly, we found that nonmitochondrial respiration (NMR) was also dramatically lowered in the Immp2l^KD−/− KO mouse. Primary mouse embryonic fibroblast (MEF) cell lines derived from the Immp2l^KD−/− KO mouse displayed a ~27% decrease in total respiration, comprising a ~50% decrease in NMR and a ~12% decrease in total mitochondrial respiration, where the latter was consistent with the cumulative decreases in substrate-specific mediated mitochondrial respiration reported here. This study is the first to report the role of Immp2l in enhancing Gpd2 structure and function, mitochondrial respiration, nonmitochondrial respiration, organ size and homeostasis. Full article

The current study compared three policosanols from Cuba (sugarcane, Raydel^®, policosanol (1), China (rice bran, Shaanxi, policosanol (2), and the USA (sugarcane, Lesstanol^®, policosanol (3) in the treatment of dyslipidemia and protection of the liver, ovary, and testis in hypercholesterolemic zebrafish. After twelve weeks of supplementation of each policosanol (PCO, final 0.1% in diet, w/w) with a high cholesterol diet (HCD, final 4%, w/w), the Raydel policosanol (PCO1) group showed the highest survivability, approximately 89%. In contrast, Shaanxi policosanol (PCO2) and Lesstanol policosanol (PCO3) produced 73% and 87% survivability, respectively, while the HCD alone group showed 75% survivability. In the 12th week, the PCO1 group demonstrated the most modest increase in body weight along with significantly lower levels of total cholesterol (TC) and triglycerides (TG) in comparison to the HCD control group. Additionally, the PCO1 group exhibited the highest proportion of high-density lipoprotein (HDL)-cholesterol within TC. Notably, the PCO1 group displayed the lowest level of aspartate aminotransferase and alanine aminotransferase, minimal infiltration of inflammatory cells, reduced interleukin (IL)-6 production in the liver, a notable decline in reactive oxygen species (ROS) generation and mitigated fatty liver changes. HCD supplementation induced impairment of kidney morphology with the greatest extent of ROS production and apoptosis. On the other hand, the PCO 1 group showed a remarkably improved morphology with the least ROS generation and apoptosis. Within the ovarian context, the PCO1 group exhibited the most substantial presence of mature vitellogenic oocytes, accompanied by minimal levels of ROS and apoptosis. Similarly, in the testicular domain, the PCO1 group showcased optimal morphology for spermatogenesis, characterized by the least interstitial area and diminished production of ROS in testicular cells. At week 8, the PCO1 group showed the highest egg-laying ability, with around 244 eggs produced per mating. In contrast, the HCD alone, PCO2, and PCO3 groups showed significantly lower egg-laying ability (49, 59, and 86 eggs, respectively). The embryos from the PCO1 group exhibited the highest survivability with the fastest swimming ability and developmental speed. These results suggest that PCO1 consumption significantly enhanced the reproduction system, egg-laying ability, and embryo survivability. In conclusion, among the three policosanols, Cuban (Raydel^®) policosanol had the strongest effect on survivability, improving dyslipidemia, liver protection, kidney, ovary, and testis with a restoration of the cell morphology, and the least ROS production and apoptosis-induced by HCD supplementation. Full article

Heavy metals such as zinc (Zn) and copper (Cu) may be associated with antibiotic resistance dissemination. Our aim was to investigate whether sub-lethal dosage of Zn and Cu may enhance plasmid transfer and subsequently resistance genes dissemination. Plasmid conjugation frequencies (PCF) were performed with Escherichia coli strains bearing IncL-bla_OXA-48, IncA/C-bla_CMY-2, IncI1-bla_CTX-M-1, IncF-bla_CTX-M-1, and IncX3-bla_NDM-5 as donors. Mating-out assays were performed with sub-dosages of zinc oxide (ZnO) and Cu sulfate (CuSO₄). Quantification of the SOS response-associated gene expression levels and of the production of reactive oxygen species were determined. Increased PCF was observed for IncL, IncA/C, and IncX3 when treated with ZnO. PCF was only increased for IncL when treated with CuSO₄. The ROS production presented an overall positive correlation with PCF after treatment with ZnO for IncL, IncA/C, and IncX3. For CuSO₄ treatment, the same was observed only for IncL. No increase was observed for expression of SOS response-associated genes under CuSO₄ treatment, and under ZnO treatment, we observed an increase in SOS response-associated genes only for IncX3. Our data showed that sub-dosages of ZnO and CuSO₄ could significantly enhance PCF in E. coli, with a more marked effect observed with IncL, IncA/C, and IncX3 scaffolds. Our study suggested that use of certain heavy metals is not the panacea for avoiding use of antibiotics in order to prevent the dissemination of antibiotic resistance. Full article

Capsaicinoids are a unique chemical species resulting from a particular biosynthesis pathway of hot chilies (Capsicum spp.) that gives rise to 22 analogous compounds, all of which are TRPV1 agonists and, therefore, responsible for the pungency of Capsicum fruits. In addition to their human consumption, numerous ethnopharmacological uses of chili have emerged throughout history. Today, more than 25 years of basic research accredit a multifaceted bioactivity mainly to capsaicin, highlighting its antitumor properties mediated by cytotoxicity and immunological adjuvancy against at least 74 varieties of cancer, while non-cancer cells tend to have greater tolerance. However, despite the progress regarding the understanding of its mechanisms of action, the benefit and safety of capsaicinoids’ pharmacological use remain subjects of discussion, since capsaicin also promotes epithelial–mesenchymal transition, in an ambivalence that has been referred to as “the double-edge sword”. Here, we update the comparative discussion of relevant reports about capsaicinoids’ bioactivity in a plethora of experimental models of cancer in terms of selectivity, efficacy, and safety. Through an integration of the underlying mechanisms, as well as inherent aspects of cancer biology, we propose mechanistic models regarding the dichotomy of their effects. Finally, we discuss a selection of in vivo evidence concerning capsaicinoids’ immunomodulatory properties against cancer. Full article

Aluminum (Al) toxicity and low pH are major factors limiting plant growth in acidic soils. Sensitive to Proton Rhizotoxicity 1 (STOP1) transcription factors respond to these stresses by regulating the expression of multiple Al- or low pH-responsive genes. ZmSTOP1-A, a STOP1-like protein from maize (Zea mays), was localized to the nucleus and showed transactivation activity. ZmSTOP1-A was expressed moderately in both roots and shoots of maize seedlings, but was not induced by Al stress or low pH. Overexpression of ZmSTOP1-A in Arabidopsis Atstop1 mutant partially restored Al tolerance and improved low pH tolerance with respect to root growth. Regarding Al tolerance, ZmSTOP1-A/Atstop1 plants showed clear upregulation of organic acid transporter genes, leading to increased organic acid secretion and reduced Al accumulation in roots. In addition, the antioxidant enzyme activity in roots and shoots of ZmSTOP1-A/Atstop1 plants was significantly enhanced, ultimately alleviating Al toxicity via scavenging reactive oxygen species. Similarly, ZmSTOP1-A could directly activate ZmMATE1 expression in maize, positively correlated with the number of Al-responsive GGNVS cis-elements in the ZmMATE1 promoter. Our results reveal that ZmSTOP1-A is an important transcription factor conferring Al tolerance by enhancing organic acid secretion and reactive oxygen species scavenging in Arabidopsis. Full article

We investigated the roles that suspicious jealousy and reactive jealousy might play in the associations between borderline personality features (BPF) and mate retention behaviors. Study 1 (N = 406) found that BPF had positive indirect associations with benefit-provisioning behaviors and cost-inflicting behaviors through suspicious jealousy but not through reactive jealousy. Study 2 (N = 334 (a dyadic sample of 167 romantic couples)) revealed actor effects such that BPF had positive indirect associations with benefit-provisioning behaviors and cost-inflicting behaviors through suspicious jealousy for both men and women. In addition, the positive association between BPF and benefit-provisioning behaviors was mediated by reactive jealousy in women but not in men. The only partner effect that emerged from these analyses showed that BPF in women were negatively associated with the benefit-provisioning behaviors reported by their male partners. Discussion focuses on the implications of these results for the function that jealousy might serve in the strategies used by individuals with BPF to maintain their romantic relationships. Full article

Mink embryos enter a period of diapause after the embryo develops into the blastocyst, and its reactivation is mainly caused by an increase in polyamine. The specific process of embryo diapause regulation and reactivation remains largely unexamined. This study aimed to identify changes in metabolites in the early pregnancy of mink by comparing and analyzing in serum metabolites up to twenty-nine days after mating. Blood samples were taken on the first day of mating, once a week until the fifth week. Metabolomic profiles of the serum samples taken during this period were analyzed by ultra-performance liquid chromatography/mass spectrometry. Multivariate statistical analyses identified differential metabolite expression at different time points in both positive and negative ion modes. The levels of dopamine, tyramine, L-phenylalanine, L-tyrosine, tyrosine, L-kynurenine, L-lysine, L-arginine, D-ornithine, and leucine changed significantly. These metabolites may be associated with the process of embryo diapause and subsequent reactivation. Full article

Hydrogen sulfide (H₂S) and related reactive sulfur species are implicated in chronic kidney disease (CKD) and hypertension. Offspring born to CKD-afflicted mothers could develop hypertension coinciding with disrupted H₂S and nitric oxide (NO) signaling pathways as well as gut microbiota. Thiosulfate, a precursor of H₂S and an antioxidant, has shown anti-hypertensive effects. This study aimed to investigate the protective effects of sodium thiosulfate (STS) in a rat model of maternal CKD-induced hypertension. Before mating, CKD was induced through feeding 0.5% adenine chow for 3 weeks. Mother rats were given a vehicle or STS at a dosage of 2 g/kg/day in drinking water throughout gestation and lactation. Perinatal STS treatment protected 12-week-old offspring from maternal CKD-primed hypertension. The beneficial effects of STS could partially be explained by the enhancement of both H₂S and NO signaling pathways and alterations in gut microbiota. Not only increasing beneficial microbes but maternal STS treatment also mediates several hypertension-associated intestinal bacteria. In conclusion, perinatal treatment with STS improves maternal CKD-primed offspring hypertension, suggesting that early-life RSS-targeting interventions have potential preventive and therapeutic benefits, awaiting future translational research. Full article

One of the problems with the doubly-fed induction generator (DFIG) is its high vulnerability to network perturbations, notably voltage dips, because of its stator windings being coupled directly to the network. As the DFIG’s stator and rotor are electromagnetically mated, the stator current peak occurs during a voltage dip causing an inrush current to the critical converter back-to-back and an overload of the DC-link capacitor. For this purpose, a series of researchers have achieved a linear and non-linear controller with a crowbar-based protection scheme. With this type of protection, the Rotor Side Converter (RSC) is disconnected momentarily, and consequently, its control of both the active and reactive output power of the stator is totally lost, leading to incorrect power quality at the point of common coupling (PCC). In this document, a robust nonlinear controller by Advanced Backstepping with Integral Action Control (ABIAC) is initially employed to monitor the rotor and the network side converters under normal network operations. In the presence of a network fault, an improved protection scheme (IPS) is tacked on to the robust nonlinear control to help enforce the behavior of the DFIG system to be able to overcome the fault. The IPS, which is formed by a crowbar and an RL series circuit, is typically located in the space between the rotor coils and the RSC converter. Compared to a standard crowbar, the developed scheme is successful to limit the rotor transient current and DC-link voltage, also an RSC disengagement to rotor windings can be prevented during the fault. Furthermore, the controllers of both the RSC and the Network Side Converter (NSC) are modified to boost the supply voltage at the PCC. A comparative study is also performed between the IPS without and with modification of the reactive power control loops. The simulation results mean that with the modified controllers during the fault, the amount of reactive power sustainment with ABIAC at the PCC is optimized to 17.5 MVAr instead of 15 MVAr with proportional-integral control (PIC). Therefore, the voltage at the PCC is fort increased in order to comply with the voltage requirements of the farm and absolutely to maintain the connection to the network in case of voltage dip. Full article

This review provides background and perspective for the articles contributing to the Special Issue of MDPI Micro-organisms on Paramecium as a Modern Model Organism. The six articles cover a variety of topics, each taking advantage of an important aspect of Paramecium biology: peripheral surface proteins that are developmentally regulated, endosymbiont algae and bacteria, ion channel regulation by calmodulin, regulation of cell mating reactivity and senescence, and the introns that dwell in the large genome. Each article highlights a significant aspect of Paramecium and its versatility. Full article