Plasma Membrane Enzyme Research Articles

Evaluation of titanium dioxide/catechol polyurethane composite for antimicrobial resistance and wastewater treatment

In this study, a novel approach for the environmentally conscious extraction of titanium dioxide from ilmenite ore while limiting the environmental impact and enhancing the advantage from an economic process. Leaching conditions were tested with different acids for effective separation of the TiO2 and were optimized concerning different experimental parameters. TiO2 and TiO2NPs were characterized using with different tools. Catechol polyurethane foam immobilized with TiO2NPs was prepared and its antimicrobial action was tested against Gram-negative bacterium E. coli, Gram-positive bacterium B. cereus, and fungus A. niger. CAT-PUF /TiO2NPs showed antimicrobial effect against E. coli, B. cereus, and A. niger with inhibition zones of 27 ± 0.14, 12 ± 0.14, and 22 ± 0.06 mm, respectively. Incorporating bioinformatics, this research contributes to the burgeoning field of nanotechnology-enabled antimicrobial materials, offering insights into the potential applications of CAT-PUF/TiO2NPs in combating microbial threats. Through bio-informatics tools, the potential toxicity of the synthesized nanoparticles was assessed, providing valuable insights into their safety profile and environmental impact. Furthermore, simulating the binding affinity between the nanoparticles and target biomolecules, such as cell membrane proteins or enzyme receptors, this aspect of the research sheds light on the mechanistic underpinnings of their antimicrobial efficacy.

6-Paradol exhibits antimicrobial, anti-quorum sensing and anti-virulence capacities on gram-negative bacteria: In vitro and in vivo studies

Grains of paradise, which are native to Africa, contain 6-paradol, an antibacterial compound found in plants of the Zingiberaceae family. In this study, the antimicrobial and anti-virulence properties of 6-paradol were evaluated against significant Gram-negative bacteria. The assessment encompassed the impact of 6-paradol on the bacterial cell membrane, efflux mechanisms, bacterial motility, biofilm formation, and extracellular enzyme production. The findings demonstrated promising anti-quorum sensing activity of 6-paradol. Moreover, the outcomes unveiled that the antimicrobial activity of 6-paradol is primarily stems from its substantial influence on the bacterial cell membrane and efflux mechanisms. Furthermore, 6-paradol exhibited potential anti-virulence activities by effectively reducing the generation of biofilm and virulent enzymes, impeding bacterial motility, and inhibiting in vivo bacterial pathogenesis. These anti-virulence effects were attributed to the compound's interference with quorum sensing systems and the downregulation of genes associated with these systems. Additionally, when combined with antibiotics, 6-paradol demonstrated synergistic effects. In conclusion, 6-paradol possesses noteworthy anti-virulence activities and can be employed as an auxiliary alongside antibiotics for treating aggressive Gram-negative infections. This highlights its potential as a valuable addition to therapeutic strategies.

The synergistic effect of biosynthesized CuONPs and phage (ϕPB2) as a novel approach for controlling Ralstonia solanacearum

BackgroundAs a vital soil-borne pathogenic bacterium, Ralstonia solanacearum can cause wilt disease in multiple Solanaceae plants. Several phages, such as ϕPB2, could infect R. solanacearum acting as a potential biological control agent in soil. In addition, some nanoparticles, especially copper preparation, also showed high toxicity on R. solanacearum with low toxicity on plant. However, whether they can be administered in combination and how effective they are in inhibiting the plant disease caused by R. solanacearum is known very little.ResultsIn this work, the characterization of CuONPs using scanning electron microscope, transmission electron microscope, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction ascertained the presence of CuONPs which were nanometer particle of 83 nm. Then it was found that combined application of CuONPs with phage (ϕPB2) was superior to that of ϕPB2 or CuONPs alone in controlling tobacco bacterial wilt, with the CuONPs (250 mg/mL) and phage (106 PFU/mL) ratio being the best, at 79.1%. The combination of CuONPs and ϕPB2 also showed no obvious toxicity on tobacco growth than control like single application of CuONPs or ϕPB2. Furthermore, the transcriptome changes of R. solanacearum analysis indicated that the combination application and single allocation of CuONPs could inhibit “biofilm formation”, molecular function, biological processes, cellular components, metabolic process, and so on. In addition, the combination application showed higher inhibition of motility and biofilm, and better enhancement of cell membrane permeability, protein leakage, MDA concentration, and enzyme activity of their respiratory chain dehydrogenase than single application of CuONPs or phage (ϕPB2). Transcriptomes analysis also supported that the addition of ϕPB2 enhanced the toxicity of CuONPs by influencing the ABC transporters and quorum sensing, metabolic processes, and cellular biosynthetic processes of R. solanacearum.ConclusionIn total, our work not only proposed a novel way to increase the bactericidal effect of nanomaterials by adding phage, but also discovered the influence, synergistic effects, and mechanisms, which is useful to design novel way to combat phytopathogenic bacteria in the complicated environment.Graphical abstract

Novel analysis of functional relationship linking moyamoya disease to moyamoya syndrome

ObjectiveThe aim of this study was to elucidate the genetic pathways associated with Moyamoya disease (MMD) and Moyamoya syndrome (MMS), compare the functional activities, and validate relevant related genes in an independent dataset. MethodsWe conducted a comprehensive search for genetic studies on MMD and MMS across multiple databases and identified related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analyses were performed for these genes. Commonly shared genes were selected for further validation in the independent dataset, GSE189993. The Sangerbox platform was used to perform statistical analysis and visualize the results. P＜0.05 indicated a statistically significant result. ResultsWe included 52 MMD and 51 MMS-related publications and identified 126 and 51 relevant genes, respectively. GO analysis for MMD showed significant enrichment in cytokine activity, cell membrane receptors, enzyme binding, and immune activity. A broader range of terms was enriched for MMS. KEGG pathway analysis for MMD highlighted immune and cellular activities and pathways related to MMS prominently featured inflammation and metabolic disorders. Notably, nine overlapping genes were identified and validated. The expressions of RNF213, PTPN11, and MTHFR demonstrated significant differences in GSE189993. A combined receiver operating characteristic curve showed high diagnostic accuracy (AUC = 0.918). ConclusionsThe findings indicate a close relationship of MMD with immune activity and MMS with inflammation, metabolic processes and other environmental factors in a given genetic background. Differentiating between MMD and MMS can enhance the understanding of their pathophysiology and inform the strategies for their diagnoses and treatment.

Elimination of representative antibiotic-resistant bacteria, antibiotic resistance genes and ciprofloxacin from water via photoactivation of periodate using FeS2

The propagation of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) induced by the release of antibiotics poses great threats to ecological safety and human health. In this study, periodate (PI)/FeS2/simulated sunlight (SSL) system was employed to remove representative ARB, ARGs and antibiotics in water. 1 × 107 CFU mL–1 of gentamycin-resistant Escherichia coli was effectively disinfected below limit of detection in PI/FeS2/SSL system under different water matrix and in real water samples. Sulfadiazine-resistant Pseudomonas and Gram-positive Bacillus subtilis could also be efficiently sterilized. Theoretical calculation showed that (110) facet was the most reactive facet on FeS2 to activate PI for the generation of reactive species (·OH, ·O2–, h+ and Fe(IV)=O) to damage cell membrane and intracellular enzyme defense system. Both intracellular and extracellular ARGs could be degraded and the expression levels of multidrug resistance-related genes were downregulated during the disinfection process. Thus, horizontal gene transfer (HGT) of ARB was inhibited. Moreover, PI/FeS2/SSL system could disinfect ARB in a continuous flow reactor and in an enlarged reactor under natural sunlight irradiation. PI/FeS2/SSL system could also effectively degrade the HGT-promoting antibiotic (ciprofloxacin) via hydroxylation and ring cleavage process. Overall, PI/FeS2/SSL exhibited great promise for the elimination of antibiotic resistance from water.

Molecular diagnosis of hereditary hemolytic anemias: Recent updates

AbstractHereditary hemolytic anemia (HHA) is a heterogeneous group of disorders due to genetically caused defects in red blood cell membrane structure, enzymes, heme and globin synthesis, erythroid proliferation, and differentiation. Traditionally, the diagnostic process is complex and includes a plethora of tests from routine to highly specialized ones. The inclusion of molecular testing has significantly improved the diagnostic yield. The value of molecular testing is broader than just rendering the correct diagnosis, as it may also guide therapeutic decisions. As more molecular modalities become available for clinical use, it is imperative to understand their benefits and disadvantages pertaining to the HHA diagnostics. Re‐evaluation of the traditional diagnostic workflow may also bring forth additional benefits. This review focuses on the current state of molecular testing for HHA.

Alteration of circulating ACE2-network related miRNAs in patients with COVID-19

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Medical University of Warsaw and São Paulo Research Foundation (FAPESP). Introduction Coronavirus disease 2019 (COVID-19) is associated with an increased risk of mortality and adverse cardiovascular (CV) occurrences, especially in a group of patients with CV diseases (CVD). SARS-CoV-2 virus enters cells through angiotensin converting enzyme 2 (ACE2) cell membrane enzymes, leading to the downregulation in the ACE2-related pathways. Based on our previous in silico [1] results we hypothesized that alteration in the ACE2 interaction network caused by virus infection can affect the expression of miRNAs and influence severity of the disease. Purpose In this study we aimed to analyse the diagnostic and predictive utility of ACE2-related miRNAs, which were identified in our previous in silico analysis (miR-10b-5p, miR-124-3p, miR-200b-3p, miR-26b-5p, miR-302c-5p) in patients with COVID-19. We also aimed to unravel the functions of analyzed miRNAs, by using machine learning based tools, including SHAP for clinical data analysis, and bioinformatic tools for data mining, target predictions and enrichment analyses. Methods Blood samples and clinical data of 79 COVID-19 patients were collected at three different time points, including the day of admission, 7-days and 21-days after admission, as well as one time-point of 32 healthy volunteers. The composite endpoint was hospitalisation length of stay (>21 days) and/or death in follow-up. Results Delta low miR-200b-3p expression (after 7-days of admission) presents predictive utility in assessment of the hospital length of stay and/or death in ROC curve analysis (AUC:0.730, p=0.002) (Fig. 1). Delta low miR-200b-3p expression, together with diabetes mellitus (DM) are independent predictors of increased hospital length of stay and/or death (OR= 5.775; CI= 1.572- 21.214; p= 0.008, OR= 4.888; CI= 1.001- 23.858; p= 0.050, respectively). The expression levels of miR-26b-5p and miR-10b-5p in COVID-19 patients were found lower at the baseline, 7 and 21-days after admission compared to the healthy controls (p<0.0001 for all time points). SHAP analysis indicated levels of miR 200b-3p (day 7th), miR-302c-5p (day 7th), CRP (day 7th), neutrophils (day 0), and D-Dimer (day 0) as the most promising predictors of long hospitalisation for the COVID-19 patients. Pathway enrichment analysis showed that among top shared pathways between targets of analyzed miRNAs were IL-2 signaling pathway, and Pathways in cancer. miR-200b-3p showed regulation of COVID-19-related targets associated with T cell protein tyrosine phosphatase and HIF-1 transcriptional activity in hypoxia, key pathways in COVID-19. Bioinformatics analysis pointed out the role of those miRNAs in multiple CVD phenotypes associated with COVID-19 (Fig. 2). Conclusions In this study we validated and characterized miRNAs which could serve as novel, predictive biomarkers of the COVID-19 long term hospitalisation and can be used for early stratification of patients and prediction of severity of infection development in an individual.

Digoxin is a potent inhibitor of Bunyamwera virus infection in cell culture.

Drug repurposing is a valuable source of new antivirals because many compounds used to treat a variety of pathologies can also inhibit viral infections. In this work, we have tested the antiviral capacity of four repurposed drugs to treat Bunyamwera virus (BUNV) infection in cell cultures. BUNV is the prototype of the Bunyavirales order, a large group of RNA viruses that includes important pathogens for humans, animals and plants. Mock- and BUNV-infected Vero and HEK293T cells were treated with non-toxic concentrations of digoxin, cyclosporin A, sunitinib and chloroquine. The four drugs inhibited BUNV infection with varying potency in Vero cells, and all except sunitinib also in HEK293T cells, with digoxin rendering the lowest half maximal inhibitory concentration (IC50). Since digoxin rendered the best results, we selected this drug for a more detailed study. Digoxin is an inhibitor of the Na+/K+ ATPase, a plasma membrane enzyme responsible for the energy-dependent exchange of cytoplasmic Na+ for extracellular K+ in mammalian cells and involved in many signalling pathways. Digoxin was shown to act at an early time point after viral entry reducing the expression of the viral proteins Gc and N. Effects on the cell cycle caused by BUNV and digoxin were also analysed. In Vero cells, digoxin favoured the transition from G1 phase of the cell cycle to S phase, an effect that might contribute to the anti-BUNV effect of digoxin in this cell type. Transmission electron microscopy showed that digoxin impedes the assembly of the characteristic spherules that harbour the BUNV replication complexes and the morphogenesis of new viral particles. Both BUNV and digoxin induce similar changes in the morphology of mitochondria that become more electron-dense and have swollen cristae. The alterations of this essential organelle might be one of the factors responsible for digoxin-induced inhibition of viral infection. Digoxin did not inhibit BUNV infection in BHK-21 cells that have a digoxin-resistant Na+/K+ ATPase, which suggests that the effects of the blockade of this enzyme is a key factor of the antiviral activity of digoxin in BUNV-infected Vero cells.

Computation-Assisted Design of ssDNA Framework Nanorobots for Cancer Logical Recognition, Toehold Disintegration, Visual Dual-Diagnosis, and Synergistic Therapy.

Single-stranded DNA (ssDNA) allows flexible and directional modifications for multiple biological applications, while being greatly limited by their poor stability, increased folding errors, and complicated sequence optimizations. This greatly challenges the design and optimization of ssDNA sequences to fold stable 3D structures for diversified bioapplications. Herein, the stable pentahedral ssDNA framework nanorobots (ssDNA nanorobots) were intelligently designed, assisted by examining dynamic folding of ssDNA in self-assemblies via all-atom molecular dynamics simulations. Assisted by two functional siRNAs (S1 and S2), two ssDNA strands were successfully assembled into ssDNA nanorobots, which include five functional modules (skeleton fixation, logical dual recognition of tumor cell membrane proteins, enzyme loading, dual-miRNA detection and synergy siRNA loading) for multiple applications. By both theoretical calculations and experiments, ssDNA nanorobots were demonstrated to be stable, flexible, highly utilized with low folding errors. Thereafter, ssDNA nanorobots were successfully applied to logical dual-recognition targeting, efficient and cancer-selective internalization, visual dual-detection of miRNAs, selective siRNA delivery and synergistic gene silencing. This work has provided a computational pathway for constructing flexible and multifunctional ssDNA frameworks, enlarging biological application of nucleic acid nanostructures.

Single-Cell Phenotyping of CD73 Expression Reveals the Diversity of the Tumor Immune Microenvironment and Reflects the Prognosis of Bladder Cancer

The cutting edge of cancer immunotherapy extends to ecto-5′-nucleotidase (CD73), a cell membrane enzyme that targets the metabolism of extracellular adenosine. We herein focused on the expression of CD73 to clarify the state of CD73 positivity in cancer immunity and tumor microenvironment, thereby revealing a new survival predictor for patients with bladder cancer (BCa). We used clinical tissue microarrays of human BCa and simultaneously performed the fluorescent staining of cell type-specific markers (CD3, CD8, Foxp3, programmed cell death protein 1, and programmed death-ligand 1 [PD-L1]) and CD73 together with DAPI for nuclear staining. In total, 156 participants were included. Multiplexed cellular imaging revealed a unique interaction between CD73 expression and CD8+ cytotoxic T cells (CTLs) and Foxp3+ regulatory T (Treg) cells in human BCa, showing the high infiltration of CD8+CD73+ CTLs and Foxp3+CD73+ Treg cells in tumors to be associated with tumorigenesis and poor prognosis in BCa. Interestingly, from a biomarker perspective, the high infiltration of CD73+ Treg cells in tumors was identified as an independent risk factor for overall survival in addition to clinicopathologic features. Regarding the relationship between immune checkpoint molecules and CD73 expression, both CD73+ CTLs and CD73+ Treg cells tended to coexpress programmed cell death protein 1 as tumor invasiveness and nuclear grade increased. Additionally, they may occupy a spatial niche located distantly from PD-L1+ cells in tumors to interfere less with the cancerous effects of PD-L1+ cells. In conclusion, the present results on the status of CD73 in cancer immunity suggest that CD73 expression on specific T-cell types has a negative immunoregulatory function. These findings may provide further insights into the immunobiological landscape of BCa, which may be translationally linked to improvements in future immunotherapy practice.

Antifungal Activity of Essential Oil and Plant-Derived Natural Compounds against Aspergillus flavus.

Aspergillus flavus is a facultative parasite that contaminates several important food crops at both the pre- and post-harvest stages. Moreover, it is an opportunistic animal and human pathogen that causes aspergillosis diseases. A. flavus also produces the polyketide-derived carcinogenic and mutagenic secondary metabolite aflatoxin, which negatively impacts global food security and threatens human and livestock health. Recently, plant-derived natural compounds and essential oils (EOs) have shown great potential in combatting A. flavus spoilage and aflatoxin contamination. In this review, the in situ antifungal and antiaflatoxigenic properties of EOs are discussed. The mechanisms through which EOs affect A. flavus growth and aflatoxin biosynthesis are then reviewed. Indeed, several involve physical, chemical, or biochemical changes to the cell wall, cell membrane, mitochondria, and related metabolic enzymes and genes. Finally, the future perspectives towards the application of plant-derived natural compounds and EOs in food protection and novel antifungal agent development are discussed. The present review highlights the great potential of plant-derived natural compounds and EOs to protect agricultural commodities and food items from A. flavus spoilage and aflatoxin contamination, along with reducing the threat of aspergillosis diseases.

Cytotoxicity Assays as Predictors of the Safety and Efficacy of Antimicrobial Agents.

The development of safe antimicrobial agents is important for the effective treatment of pathogens. From a multitude of discovered inhibitory compounds, only a few antimicrobial agents are able to enter the market. Many antimicrobials are, on the one hand, quite effective in killing pathogens but, on the other hand, cytotoxic to eukaryotic cells. Cell health can be monitored by various methods. Plasma membrane integrity, DNA synthesis, enzyme activity, and reducing conditions within the cell are known indicators of cell viability and cell death. For a comprehensive overview, methods to analyze cytotoxic and hemolytic effects, e.g., lactate dehydrogenase release, cell proliferation analysis, cell viability analysis based on the activity of different intracellular enzymes, and hemolysis assay of antimicrobial compounds on human cells, are described in this updated chapter.

A Retrospective Comparative Study of Sodium Fluoride Na18F-PET/CT and 68Ga-PSMA-11 PET/CT in the Bone Metastases of Prostate Cancer Using a Volumetric 3-D Radiomic Analysis.

Bone is the most common metastatic site in prostate cancer (PCa). 68Ga-PSMA-11 (or gozetotide) and sodium fluoride-18 (Na18F) are rather new radiopharmaceuticals for assessing PCa-associated bone metastases. Gozetotide uptake reflects cell membrane enzyme activity and the sodium fluoride uptake measures bone mineralization in advanced PCa. Here, we aim to characterize this difference and possibly provide a new method for patient selection in targeted therapies. Methods: The study consisted of 14 patients with advanced PCa (M group > 5 lesions), who had had routine PET/CT both with PSMA and NaF over consecutive days, and 12 PCa patients with no skeletal metastases (N). The bone regions in CT were used to coregister the two PET/CT scans. The whole skeleton volume(s) of interest (VOIs) were defined using the CT component of PET (HU > 150); similarly, the sclerotic/dense bone was defined as HU > 600. Additional VOIs were defined for PET, with pathological threshold values for PSMA (SUV > 3.0) and NaF (SUV > 10). Besides the pathological bone volumes measured with each technique (CT, NaF, and PSMA-PET) and their contemporaneous combinations, overlapping VOIs with the CT-based skeletal and sclerotic volumes were also recorded. Additionally, thresholds of 4.0, 6.0, and 10.0 were tested for SUVPSMA. Results: In group M, the skeletal VOI volumes were 8.77 ± 1.80 L, and the sclerotic bone volumes were 1.32 ± 0.50 L; in contrast, in group N, they were 8.73 ± 1.43 L (skeletal) and 1.23 ± 0.28 L (sclerosis). The total enzyme activity for PSMA was 2.21 ± 5.15 in the M group and 0.078 ± 0.053 in the N group (p < 0.0002). The total bone demineralization activity for NaF varied from 4.31 ± 6.17 in the M group and 0.24 ± 0.56 in group N (p < 0.0002). The pathological PSMA volume represented 0.44−132% of the sclerotic bone volume in group M and 0.55−2.3% in group N. The pathological NaF volume in those patients with multiple metastases represented 0.27−68% of the sclerotic bone volume, and in the control group, only 0.00−6.5% of the sclerotic bone volume (p < 0.0003). Conclusions: These results confirm our earlier findings that CT alone does not suit the evaluation of the extent of active skeletal metastases in PCa. PSMA and NaF images give complementary information about the extent of the active skeletal disease, which has a clinical impact and may change its management. The PSMA and NaF absolute volumes could be used for planning targeted therapies. A cut-off value 3.0 for SUVPSMA given here is the best correlation in the presentation of active metastatic skeletal disease.

Abnormal maternal behavior in mice lacking phospholipase Cβ1

ABSTRACT Motherhood goes through preparation, onset and maintenance phases until the natural weaning. A variety of changes in hormonal/neurohormonal systems and brain circuits are involved in the maternal behavior. Hormones, neuropeptides, and neurotransmitters involved in maternal behavior act via G-protein-coupled receptors, many of which in turn activate plasma membrane enzymes including phospholipase C (PLC) β isoforms. In this study, we examined the effect of PLCβ1 knockout (KO) on maternal behavior. There was little difference between PLCβ1-KO and wild-type (WT) dams in the relative time spent in maternal behavior during the period between 24 h prepartum and 12 h postpartum (−24 h ∼ PPH 12). After PPH 18, however, PLCβ1-KO dams neglected their pups so that they all died in 2–3 days. In the pup retrieval test, latency was not different during the period within PPH 12, but after PPH 18, PLCβ1-KO dams could not finish pup retrieval in a given time. During both periods, FosB expression in the nucleus accumbens (NAcc) of PLCβ1-KO dams was significantly lower than WT, but not different in the medial preoptic area (mPOA). Given that mPOA activity is required for initiation of maternal behavior, and that NAcc is known to be involved in maternal motivation and maintenance of maternal behavior, our results suggest that PLCβ1 signaling is essential for transition from the onset to maintenance phase of maternal behavior.

Gangliosides and Cell Surface Ganglioside Metabolic Enzymes in the Nervous System.

Gangliosides are a large group of complex lipids found predominantly in the outer layer of the plasma membrane of cells, particularly abundant in nerve endings. Their half-life in the nervous system is short, and their membrane composition and content are strictly connected to their metabolism. The neobiosynthesis of gangliosides starts in the endoplasmic reticulum and is completed in the Golgi apparatus, whereas catabolism occurs primarily in lysosomes. However, the final content of gangliosides in the plasma membrane is defined by other cellular processes.This chapter will discuss structural changes in the oligosaccharide chains of gangliosides, induced by the activity of plasma membrane-associated glycohydrolases and glycosyltransferases. Some of the plasma membrane enzymes originate from fusion processes between intracellular fractions and the plasma membrane, while, others display a different structure. Several of these plasma membrane enzymes have been characterized and some of them seem to have a specific role in the nervous system.

Thyroid hormones: Metabolism and transportation in the fetoplacental unit.

The thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3), are of vital importance for fetal development. The concentration of THs in fetal circulation varies throughout gestation and differs from the concentration in the maternal serum, indicating the presence of maternal-fetal thyroid homeostasis regulatory mechanisms in the placenta. The passage of THs from maternal circulation to fetal circulation is modulated by plasma membrane transporters, enzymes, and carrier proteins. Monocarboxylate transporter 8, iodothyronine deiodinases (DIO2 and DIO3), and transthyretin are especially involved in this maternal-fetal thyroid modulation, shown by a greater expression in the placenta. THs also play a role in placental development and as expected, abnormal variations in TH levels are associated with pregnancy complications and can result in damage to the fetus. Although new evidence regarding TH regulation during pregnancy and its effects in the mother, placenta, and fetus has been published, many aspects of these interactions are still poorly understood. The objective of this review is to provide an evidence-based update, drawn from current data, on the metabolism and transport of THs in the placenta and their vital role in the maternal-fetal relationship.

Abscisic acid: Metabolism, transport, crosstalk with other plant growth regulators, and its role in heavy metal stress mitigation.

Heavy metal (HM) stress is threatening agricultural crops, ecological systems, and human health worldwide. HM toxicity adversely affects plant growth, physiological processes, and crop productivity by disturbing cellular ionic balance, metabolic balance, cell membrane integrity, and protein and enzyme activities. Plants under HM stress intrinsically develop mechanisms to counter the adversities of HM but not prevent them. However, the exogenous application of abscisic acid (ABA) is a strategy for boosting the tolerance capacity of plants against HM toxicity by improving osmolyte accumulation and antioxidant machinery. ABA is an essential plant growth regulator that modulates various plant growth and metabolic processes, including seed development and germination, vegetative growth, stomatal regulation, flowering, and leaf senescence under diverse environmental conditions. This review summarizes ABA biosynthesis, signaling, transport, and catabolism in plant tissues and the adverse effects of HM stress on crop plants. Moreover, we describe the role of ABA in mitigating HM stress and elucidating the interplay of ABA with other plant growth regulators.

Dysregulated Metabolism in Cancer

Metabolism describes the cellular bioenergetic pathways that provide energy and macromolecules for protein, lipid, and nucleic acid syntheses. In cancer, malignant cells alter the metabolic pathways to acquire nutrients needed for proliferation and survival. The various metabolic modifications exhibited by cancer cells include aerobic glycolysis, decreased oxidative phosphorylation, and elevated production of biosynthetic intermediates. To support the increasing need for these metabolic modifications, cancer cells increase the expressions of plasma membrane transporters and enzymes involved in the metabolic pathways. Additionally, some cancer cells escape chemotherapy treatment by reprogramming their metabolic activities. This chemotherapy-induced resistance mechanism allows malignant cells to promote their survival as well as to provide defense against cell damage by engaging various metabolic shunt pathways. Therefore, understanding metabolic reprogramming in cancer may provide useful information that can further be exploited to strategize potential treatment interventions and subsequently foster better outcomes among patients with cancer.

Pengaruh Pemberian Jus Buah Sirsak (Annona Muricata Linn) Terhadap Kadar Malondialdehyde (MDA) Plasenta Tikus Putih Strain Wistar (Rattus novergicus) Bunting dengan Paparan Asap Rokok)

Cigarettes contain many toxic free radicals and reactive oxygen species (ROS) which can trigger cell membrane lipids, proteins, enzymes, and DNA to undergo oxidative damage. The amount of ROS (reactive oxygen species) during pregnancy can increase if pregnant women are exposed to cigarette smoke which are toxic due to the risk of oxidative stress so as to form Malondialdehyde (MDA) compounds caused by lipid peroxidation. Lipid peroxidation and increased levels of MDA can cause damage to cell membranes, one of which is the placental endothelial cell membrane. The content of vitamin C and sufficient polyphenols in soursop has the potential as a source of antioxidants that can inhibit or slow down the formation of free radicals and ROS. Objective: To determine the benefits or effect of giving soursop fruit juice (Annona muricata Linn) on the placental MDA levels of pregnant rats with wistar strain (Rattus norvegicus) exposed to cigarette smoke. Methods: A true experimental laboratory with a randomized posttest-only control group design. Different doses of exposure to cigarette smoke and soursop juice were selected at random and divided into 3 treatment groups and 2 control groups. Giving soursop fruit juice was carried out on the first day until the nineteenth day of pregnancy, while cigarette smoke was exposed on the seventh day until the nineteenth day of pregnancy. Results: The significance value calculated by the Kruskal-Wallis test was 0.350 (p&gt;0.05), which showed that there was no significant effect on the MDA value of the placenta of pregnant rats given soursop fruit juice and exposed to cigarette smoke. Conclusion: Soursop fruit juice with a dose of 0.5gr/200gr BW/day can prevent the increase in MDA levels of pregnant rat placenta exposed to cigarette smoke.

The ctpF Gene Encoding a Calcium P-Type ATPase of the Plasma Membrane Contributes to Full Virulence of Mycobacterium tuberculosis.

Identification of alternative attenuation targets of Mycobacterium tuberculosis (Mtb) is pivotal for designing new candidates for live attenuated anti-tuberculosis (TB) vaccines. In this context, the CtpF P-type ATPase of Mtb is an interesting target; specifically, this plasma membrane enzyme is involved in calcium transporting and response to oxidative stress. We found that a mutant of MtbH37Rv lacking ctpF expression (MtbΔctpF) displayed impaired proliferation in mouse alveolar macrophages (MH-S) during in vitro infection. Further, the levels of tumor necrosis factor and interferon-gamma in MH-S cells infected with MtbΔctpF were similar to those of cells infected with the parental strain, suggesting preservation of the immunogenic capacity. In addition, BALB/c mice infected with Mtb∆ctpF showed median survival times of 84 days, while mice infected with MtbH37Rv survived 59 days, suggesting reduced virulence of the mutant strain. Interestingly, the expression levels of ctpF in a mouse model of latent TB were significantly higher than in a mouse model of progressive TB, indicating that ctpF is involved in Mtb persistence in the dormancy state. Finally, the possibility of complementary mechanisms that counteract deficiencies in Ca2+ transport mediated by P-type ATPases is suggested. Altogether, our results demonstrate that CtpF could be a potential target for Mtb attenuation.