Cytotoxic and Apoptotic Effects of Green Synthesized Silver Nanoparticles via Reactive Oxygen Species-Mediated Mitochondrial Pathway in Human Breast Cancer Cells.

Due to their exceptional physicochemical features, green synthesized silver nanoparticles (AgNPs) have been of considerable interest in cancer treatment. In the present study, for the first time, we aimed to green synthesize AgNPs from Euphorbia retusa and explore their anticancer potential on human breast cancer (MCF-7) cells. First, the green synthesized AgNPs (EU-AgNPs) were well characterized by UV-visible spectroscopy, Fourier transmission infrared (FTIR) spectrum, XRD, scanning and transmission electron microscopy (SEM and TEM), and EDX techniques. The characterization data exhibited that EU-AgNPs were spherical in shape and crystalline in nature with an average size of 17.8 nm. FTIR results established the presence of active metabolites in EU-AgNPs. Second, the anticancer effect of EU-AgNPs was evaluated against MCF-7 cells by MTT and neutral red uptake (NRU) assays. Moreover, morphological changes, ROS production, MMP, and apoptotic marker genes were also studied upon exposure to cytotoxic doses of EU-AgNPs. Our results showed that EU-AgNPs induce cytotoxicity in a concentration-dependent manner, with an IC50 value of 40 µg/mL. Morphological changes in MCF-7 cells exposed to EU-AgNPs also confirm their cytotoxic effects. Increased ROS and decreased MMP levels revealed that EU-AgNPs induced oxidative stress and mitochondrial membrane dysfunction. Moreover, ROS-mediated apoptosis was confirmed by elevated levels of proapoptotic marker genes (p53, Bax, caspase-3, and caspase-9) and reduced levels of an antiapoptotic gene (Bcl-2). Altogether, these findings suggested that EU-AgNPs could induce potential anticancer effects through ROS-mediated apoptosis in MCF-7 cells.

Detection of Hepatitis E Virus (HEV) Among Ruminant Animals.

BACKGROUND: HEV is endemic in several Middle Eastern countries including Saudi Arabia, which hosts the annual pilgrimage for Muslims from around the world. One of the Hajj rituals is the sacrifice of animals, including camels, cows, goats, and sheep. HEV Zoonosis is established in swine and other suspected species, including deer, rabbits, dromedary, and Bactrian camels. HEV was identified in small, domesticized animals like goats, cows, sheep, and horses. We previously investigated HEV seroprevalence in Camels. This study aimed to evaluate HEV seroprevalence in other highly consumed ruminants in Saudi Arabia, namely cows, sheep, and goats. METHODS: Sera from cows (n = 47), goats (n = 56), and sheep (n = 67) were analyzed for the presence of HEV-IgG by using in-house developed ELISA assays. RESULTS: The highest seroprevalence was found in sheep (62.7%), followed by cows (38.3%), and then goats (14.3%), with a p-value of < 0.001. No other demographic characteristics of the animals were significantly correlated with the HEV seroprevalence. CONCLUSIONS: This study provides baseline data as the first study on the seroprevalence of HEV in ruminant animals in Saudi Arabia. The high seroprevalence found in sheep and cows must be further investigated for the potential zoonotic HEV transmission to humans. Further studies are needed to investigate the active viremia in these animal species through nucleic acid detection and sequencing to provide data on the circulating HEV genotypes among the targeted animal species. The detection of HEV in different animal products, such as milk, liver, and others, also remains an important study area to consider.

Novel 3,6-Disubstituted Pyridazine Derivatives Targeting JNK1 Pathway: Scaffold Hopping and Hybridization-Based Design, Synthesis, Molecular Modeling, and In Vitro and In Vivo Anticancer Evaluation.

A series of novel 3,6-disubstituted pyridazine derivatives were designed, synthesized, and biologically evaluated as preclinical anticancer candidates. Compound 9e exhibited the highest growth inhibition against most of the NCI-60 cancer cell lines. The in vivo anticancer activity of 9e was subsequently investigated at two dose levels using the Ehrlich ascites carcinoma solid tumor animal model, where a reduction in the mean tumor volume allied with necrosis induction was reported without any signs of toxicity in the treated groups. Interestingly, compound 9e was capable of downregulating c-jun N-terminal kinase-1 (JNK1) gene expression and curbing the protein levels of its phosphorylated form, in parallel with a reduction in its downstream targets, namely, c-Jun and c-Fos in tumors, along with restoring p53 activity. Furthermore, molecular docking and dynamics simulations were carried out to predict the binding mode of 9e and prove its stability in the JNK1 binding pocket.

Association of MTR and MTRR polymorphisms with recurrent pregnancy loss: a case control study.

BACKGROUND: In light of several epidemiological studies, the etiology of recurrent pregnancy loss is complex. One of the most frequent causes of women experiencing inexplicable recurrent pregnancy loss is maternal thrombophilia. Hence, the association between genetic polymorphisms causing thrombophilia and recurrent pregnancy loss needs to be explored. AIM: Is to study the relation of polymorphisms affecting folate pathway mainly, 5-Methytetrahydrofolate-Homocysteine Methyltransferase (MTR A2756G) and 5-Methytetrahydrofolate-Homocysteine MethyltransferaseReductase (MTRR A66G) with recurrent pregnancy loss. METHODS: It is a case-control study. Four hundred participants were enrolled. Two hundred participants with unexplained recurrent pregnancy loss (case group) and two hundred healthy fertile participants (control group). All participants were screened for (MTR A2756G) and (MTRR A66G). DNA was extracted using salting out method followed by genotyping via Real-time PCR. RESULTS: Mutant homozygous genotype (GG) in MTRR A66G was statistically significantly among RPL group in comparison to controls. (GG vs. AA) had odds ratio and confidence interval of 1.22(1.12-2.23), P = 0.012. (GG) increased the liability 1.2 folds for recurrent pregnancy loss. Mutant homozygous genotype (GG) in MTR A2756G was not correlated with the risk of recurrent pregnancy loss. (GG vs.AA) = (1.13(0.56-2.29)), P = 0.7 CONCLUSION: MTRR A66G increases susceptibly for recurrent pregnancy loss among Egyptian women.

Preparation, Characterization, In Vitro Biological Evaluation, DFT Calculations, and Molecular Docking Investigations of 1H-Imidazole-2-Carboxylic acid and Histidine-Based Mixed-Ligand Complexes.

Mixed-ligand complexes incorporating 1H-Imidazole-2-Carboxylic acid (IMCA) and Histidine (LHIS) show promise for biomedical and biotechnological applications. This study synthesizes and characterizes FeIMCALHIS, CoIMCALHIS, and NiIMCALHIS coordination compounds using metal chloride salts (FeCl3.6H2O, CoCl2.6H2O, NiCl2.6H2O) in ethanolic solutions. The complexes are characterized by spectroscopic methods (IR, UV-vis, and mass spectra), elemental analysis, conductivity, magnetic, and thermal analysis. Molar conductivity indicates their non-electrolytic nature. UV-vis spectra reveal absorption bands with pathochromic shifts, and electronic spectra show characteristic metal-ligand transitions, indicating their structural configuration and coordination geometry. 3D geometry optimization shows six-coordination around Fe(III) and Co(II) in FeIMCALHIS and CoIMCALHIS, and four-coordination around Ni(II) in NiIMCALHIS. Analysis of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) suggests decreased electron donation ability upon coordination. Electronic structure parameters (HOMO, LUMO, ionization potential, energy gap, electron affinity, chemical potentials, and electronegativity) provide further insights into stability and reactivity. The metal complexes exhibit enhanced antimicrobial, antioxidant, and anti-inflammatory activity compared to individual ligands, with FeIMCALHIS showing notable antimicrobial activity. Molecular docking analysis reveals strong binding interactions with target proteins, highlighting their potential therapeutic applications.

Cilostazol attenuates mirabegron-induced hepatic and renal toxicity in rats: regulation of metabolic, oxidative, and inflammatory pathways.

BACKGROUND: Mirabegron (MIRG) is a type of ß3 adrenoceptor agonist that is considered an alternative therapy for the treatment of overactive bladder (OAB) symptoms. Cilostazol (CITZ) is a selective inhibitor of phosphodiesterase (III) that has various pharmacological effects. OBJECTVE: The current study aimed to highlight the regulatory effects of CITZ on MIRG-induced toxicity. MATERIALS AND METHODS: Male rats were divided into six groups. Blood samples were collected to determine different hepatic and kidney function levels along with serum protein electrophoresis and inflammatory factor levels. Histopathological studies and oxidative stress (OS) were also assessed. Kidney and hepatic damage were detected following the administration of MIRG, especially at high doses, due to elevated OS, inflammation, and apoptotic marker levels. RESULTS: Rats receiving CITZ exhibited significant improvements in both hepatic and kidney functions, with decreased inflammation and OS. CONCLUSION: CITZ administration plays a beneficial role in alleviating hepatic and nephrotoxicity induced by MIRG by inhibiting OS and inflammation.

Exploring the anti-protozoal mechanisms of Syzygium aromaticum phytochemicals targeting Cryptosporidium parvum lactate dehydrogenase through molecular dynamics simulations.

Cryptosporidium parvum (C. parvum), a protozoan parasite, is known to induce significant gastrointestinal disease in humans. Lactate dehydrogenase (LDH), a protein of C. parvum, has been identified as a potential therapeutic target for developing effective drugs against infection. This study utilized a computational drug discovery approach to identify potential drug molecules against the LDH protein of C. parvum. In the present investigation, we conducted a structure-based virtual screening of 55 phytochemicals from the Syzygium aromaticum (S. aromaticum). This process identified four phytochemicals, including Gallotannin 23, Eugeniin, Strictinin, and Ellagitannin, that demonstrated significant binding affinity and dynamic stability with LDH protein. Interestingly, these four compounds have been documented to possess antibacterial, antiviral, anti-inflammatory, and antioxidant properties. The docked complexes were simulated for 100 ns using Desmond to check the dynamic stability. Finally, the free binding energy was computed from the last 10ns MD trajectories. Gallotannin 23 and Ellagitannin exhibited considerable binding affinity and stability with the target protein among all four phytochemicals. These findings suggest that these predicted phytochemicals from S. aromaticum could be further explored as potential hit candidates for developing effective drugs against C. parvum infection. The in vitro and in vivo experimental validation is still required to confirm their efficacy and safety as LDH inhibitors.

Hepatoprotective effect of date fruit extract against ethanol-induced apoptosis in human hepatoma (HepG2) cells.

Ethanol is a well-known hepatotoxic agent and date fruits have been associated with their biological actions. In current study, we have investigated the hepatoprotective potential of DFE on ethanol-induced cellular damages in human hepatoma (HepG2) cells. The hepatoprotective potential was assessed by exposing the HepG2 cells to non-toxic concentrations (15, 30, and 60 µg/mL) of DFE for 24 h; then toxic concentration (500 µM) of ethanol. Our results demonstrated that pretreatment with DFE significantly prohibited ethanol-induced hepatotoxicity in HepG2 cells. We observed that DFE treatment increased cell viability, reduced LDH leakage, restored cellular morphology, and inhibited caspase-3 enzyme activity in a dose dependent way, induced by ethanol. Further DFE was also effective in restoring the LPO, GSH, and catalase levels towards normal altered by ethanol. Our results also revealed that ethanol-induced ROS generation was significantly inhibited by DFE. The ethanol-induced mRNA expression of apoptotic related genes (p53, caspase-3, caspase-7, Bax, and Bcl-2) were also normalized by pretreatment with DFE. The findings from this study indicated that DFE can significantly protect HepG2 cells against ethanol-induced hepatotoxicity. Our study also provides scientific validation for the traditional use of DFE, aiming to understand its hepatoprotective potential. Altogether, to the best of our knowledge, this is the first study demonstrated that ethanol-induced hepatotoxicity can be prohibited by the DFE. Thus, DFE has a potential application in nutraceuticals as a therapeutic agent to prevent liver diseases.

Novel Insights into the Antimicrobial and Antibiofilm Activity of Pyrroloquinoline Quinone (PQQ); In Vitro, In Silico, and Shotgun Proteomic Studies.

Microbial infections pose a significant global health threat, affecting millions of individuals and leading to substantial mortality rates. The increasing resistance of microorganisms to conventional treatments requires the development of novel antimicrobial agents. Pyrroloquinoline quinone (PQQ), a natural medicinal drug involved in various cellular processes, holds promise as a potential antimicrobial agent. In the present study, our aim was, for the first time, to explore the antimicrobial activity of PQQ against 29 pathogenic microbes, including 13 fungal strains, 8 Gram-positive bacteria, and 8 Gram-negative bacteria. Our findings revealed potent antifungal properties of PQQ, particularly against Syncephalastrum racemosum, Talaromyces marneffei, Candida lipolytica, and Trichophyton rubrum. The MIC values varied between fungal strains, and T. marneffei exhibited a lower MIC, indicating a greater susceptibility to PQQ. In addition, PQQ exhibited notable antibacterial activity against Gram-positive and -negative bacteria, with a prominent inhibition observed against Staphylococcus epidermidis, Proteus vulgaris, and MRSA strains. Remarkably, PQQ demonstrated considerable biofilm inhibition against the MRSA, S. epidermidis, and P. vulgaris strains. Transmission electron microscopy (TEM) studies revealed that PQQ caused structural damage and disrupted cell metabolism in bacterial cells, leading to aberrant morphology, compromised cell membrane integrity, and leakage of cytoplasmic contents. These findings were further affirmed by shotgun proteomic analysis, which revealed that PQQ targets several important cellular processes in bacteria, including membrane proteins, ATP metabolic processes, DNA repair processes, metal-binding proteins, and stress response. Finally, detailed molecular modeling investigations indicated that PQQ exhibits a substantial binding affinity score for key microbial targets, including the mannoprotein Mp1P, the transcriptional regulator TcaR, and the endonuclease PvuRTs1I. Taken together, our study underscores the effectiveness of PQQ as a broad-spectrum antimicrobial agent capable of combating pathogenic fungi and bacteria, while also inhibiting biofilm formation and targeting several critical biological processes, making it a promising therapeutic option for biofilm-related infections.

Fabrication of smart nanogel based on carrageenan and green coffee extract as a long-term antifouling agent to improve biofilm prevention in food production.

This study investigates the extract of the bioactive compounds from green coffee extract (GCE) and the loading of two different concentrations of GCE (1% and 2%) onto carrageenan nanogels (CAR NGs) to compare their antibacterial and antibiofilm effects with unloaded nanogels (NGs). The bioactive compounds of GCE were characterized using GC-MS analysis. The GCE1 and GCE2 were successfully deposited onto the surface of CAR NGs. The antibacterial and antibiofilm potential of prepared NGs were conducted against some foodborne pathogens (E. coli O157, Salmonella enterica, Staphylococcus aureus, and Listeria monocytogenes). The results of GC-MS analysis indicated that there were identified 16 bioactive compounds in GCE, including caffeine (36.27%), Dodemorph (9.04%), and D-Glycero-d-ido-heptose (2.44%), contributing to its antimicrobial properties. The antibacterial coatings demonstrated a notable antimicrobial effect, showing zone of inhibition (ZOI) diameters of up to 37 mm for GCE2 loaded CAR NGs. The minimum inhibitory concentration (MIC) values for GCE2 loaded CAR NGs were 80 ppm for E. coli O157, and 120 ppm for S. enterica, S. aureus, and L. monocytogenes, achieving complete bacterial inactivation within 10-15 min of exposure. Both GCE1 and GCE2 loaded CAR NGs significantly reduced biofilm cell densities on stainless steel (SS) materials for E. coli O157, S. enterica, S. aureus, and L. monocytogenes, with reductions ranging from 60% to 95%. Specifically, biofilm densities were reduced by up to 95% for E. coli O157, 89% for S. enterica, 85% for S. aureus, and 80% for L. monocytogenes. Results of the toxicity evaluation indicated that the NGs were non-toxic and biocompatible, with predicted EC50 values proved their biocompatibility and safety. These results recommended that GCE loaded CAR NGs are promising as natural antimicrobial agents for enhancing food safety and extending shelf life. Further, the study concluded that incorporating GCE into CAR NGs is an effective strategy for developing sustainable antimicrobial coatings for the food industry and manufacturing.

Marine fungal diversity unlocks potent antivirals against monkeypox through methyltransferase inhibition revealed by molecular dynamics and free energy landscape.

The escalating threat posed by the Monkeypox virus (MPXV) to global health necessitates the urgent discovery of effective antiviral agents, as there are currently no specific drugs available for its treatment, and existing inhibitors are hindered by toxicity and poor pharmacokinetic profiles. This study aimed to identify potent MPXV inhibitors by screening a diverse library of small molecule compounds derived from marine fungi, focusing on the viral protein VP39, a key methyltransferase involved in viral replication. An extensive virtual screening process identified four promising compounds-CMNPD15724, CMNPD28811, CMNPD30883, and CMNPD18569-alongside a control molecule. Rigorous evaluations, including re-docking, molecular dynamics (MD) simulations, and hydrogen bond analysis, were conducted to assess their inhibitory potential against MPXV VP39. CMNPD15724 and CMNPD30883, in particular, demonstrated a superior binding affinity and stable interactions within the target protein's active site throughout the MD simulations, suggesting a capacity to overcome the limitations associated with sinefungin. The stability of these VP39-compound complexes, corroborated by MD simulations, provided crucial insights into the dynamic behavior of these interactions. Furthermore, Principal Component Analysis (PCA) based free energy landscape assessments offered a detailed understanding of the dynamic conformational changes and energetic profiles underlying these compounds' functional disruption of VP39. These findings establish CMNPD15724, CMNPD28811, CMNPD30883, and CMNPD18569 as promising MPXV inhibitors and highlight marine fungi as a valuable source of novel antiviral agents. These compounds represent potential candidates for further experimental validation, advancing the development of safer and more effective therapeutic options to combat this emerging viral infection.

Premenstrual syndrome among medical versus non-medical workers and its association with work-related quality of life.

BACKGROUND: Premenstrual syndrome (PMS) is a commonly underestimated disorder that negatively impacts a woman's life. Medical workers, who live a more stressful life, may report an increased rate of PMS. Studies on the relationship between PMS and work-related quality of life for medical professionals are scarce, particularly in the Arab world. This study aimed to compare the frequency of PMS among medical versus non-medical workers at Zagazig University and to assess the association between PMS and their work-related quality of life. METHODS: A comparative cross-sectional study was conducted. The sample population consisted of 48 medical and 48 non-medical female workers aged 18-45 years from Zagazig University. The two groups filled out a questionnaire with 3 parts: sociodemographic and occupational data, the Premenstrual Symptoms Screening Tool (PSST), and the Work-Related Quality of Life Scale (WRQL). RESULTS: Severe PMS was reported in 45.8% of medical workers versus 20.8% of non-medical workers with a statistically significant difference between both groups (p = 0.009). Binary logistic regression showed that being a medical worker, clinical specialty, ≥ 8 years of work, ≥ 24 working hours per week, and having a non-set hourly schedule were predictors for severe PMS. PMS was found to be a statistically significant predictor of poor WRQL (p < 0.001). There was a highly significant negative correlation between the PMS score and the WRQL score (r = - 0.302, p < 0.001). CONCLUSION: Among medical workers, PMS is more common and more severe, and WRQL is worse and negatively correlated with PMS. We suggest further studies with larger samples to prove this association and planning for public health programs to screen for and manage PMS among medical workers in our community.

A clinical study and laboratory evaluation of the cardiac and hepatic toxic effects of paraphenylenediamine.

INTRODUCTION: Paraphenylenediamine is the main component in many commercial hair dyes, and can produce severe local and systemic toxicity reactions after acute ingestion or dermal absorption. The aim of this study was to assess the factors contributing to morbidity and mortality in cases of acute paraphenylenediamine poisoning, with a focus on evaluating the resultant hepatic and cardiac toxicity. METHODS: This observational study was conducted on patients with acute paraphenylenediamine poisoning presenting to Sohag University Hospitals, and included a retrospective part from February 2021 to January 2022 and a prospective part from February 2022 to July 2022. Clinical data were extracted and receiver operating characteristic curves created to identify prognostic markers. RESULTS: Among 50 eligible patients 39 (78 percent) recovered, and 11 (22 percent) died or had permanent complications. Angioedema and anuria were the most frequent features in complicated cases. By receiver operating characteristic analysis, either an increase in aspartate aminotransferase activity greater than 644 IU/L or alanine aminotransferase activity greater than 798 IU/L, a time delay to presentation of greater than 4.5 hours, and a pH of less than 7.32 were associated with a significant increase in morbidity and mortality. While cardiac enzyme activities, and concentrations of blood urea nitrogen and creatinine increased in most cases, they were not associated with mortality. DISCUSSION: Management of patients with paraphenylenediamine poisoning is mainly supportive, as there is no specific antidote. Respiratory failure and kidney failure are the most life threatening complications. Hepatoxicity and cardiotoxicity also occur. The ability to predict the events can help guide patient disposition and care. CONCLUSION: Elevated liver enzyme activities, increased time delay to admission, decreased pH, and the presence of angioedema and anuria can be used as predictors of morbidity and mortality in patients with acute paraphenylenediamine poisoning.

New prospective insecticidal agents based on N-(arylcarbamothioyl)arylmide derivatives against Spodoptera frugiperda: Design, Synthesis, Toxicological, Biological, Biomedical Studies and Antibacterial Activity.

In this work, a novel series of N-(arylcarbamothioyl)arylmide) 2-11 were synthesized by treating One-Pot three-multicomponent of Aroyl chloride ammonium isothiocyanate and amine compounds under refluxing conditions. Using spectroscopic methods, the chemical structure of the novelty developed compounds were investigated. After five days, the proposed derivatives' insecticidal bioassay was assessed using the median lethal concentration (LC50) against the second & fourth larvae of Spodoptera frugiperda as toxicity agents. The findings showed that, to varying degrees, every tested substance exerted insecticidal effects on S. frugiperda larvae in both of their instars. Compound 9 was the most poisonous of them all, having an LC50 against larvae in their second and fourth instars of 60.45 and 123.21 mg/L, respectively. Additionally, a few biological and biochemical characteristics of the substances that were generated in a lab setting were also looked at. Furthermore, this work discusses how to discover novel compounds that may one day be employed as insecticidal agents. Finally, all the designed components were monitored for their antibacterial effectiveness toward both Gram-positive & Gram-negative bacteria.

Preparation of thermochromic ink from anthocyanidin-encapsulated alginate nanoparticles for anticounterfeiting applications.

In order to make commercial products less vulnerable to counterfeiting, thermochromic inks have proven to be a viable authentication strategy. Herein, we developed a thermochromic ink for authentication by combining an anthocyanidin (ACYD) extract with alginate (ALG). To increase the anthocyanidin/alginate ink stability, a mordant (ferrous sulfate) was employed to tie up the anthocyanidin biomolecules with alginate. ACYD was extracted from red-cabbage and then immobilized into alginate to serve as an environmentally friendly spectroscopic probe. Thermochromic composite inks (ACYD@ALG) were made by adjusting the content of anthocyanidin. A homogenous blue film (608 nm) was printed on a paper surface and investigated by the CIE Lab coordinate system. The blue color transformed into reddish (477 nm) when heated from 35°C to 65°C. Nanoparticles (NPs) of anthocyanidin/mordant (ACYD/M) were examined for their size and morphology to indicate diameters of 80-90 nm, whereas the ACYD/M-encapsulated alginate nanoparticles showed diameters of 120-150 nm. Multiple analytical techniques were utilized to examine the printed papers. The mechanical and rheological performance of both stamped sheets and ink fluid were explored. The cytotoxicity and antimicrobial efficacy of ink (ACYD@ALG) were investigated.

Gestationally administered RAS modulators reprogram endotoxic cardiovascular and inflammatory profiles in adult male offspring of preeclamptic rats.

Previous studies showed that preeclampsia (PE) amplifies cardiovascular dysfunction induced by endotoxemia in adult male, but not female, offspring. Here, we asked if such aggravated endotoxic insult could be nullified by modulators of the renin-angiotensin system (RAS). PE was induced by gestational administration of Nω-nitro-L-arginine methyl ester(L-NAME, a nitric oxide synthase inhibitor). Adult male offspring of PE mothers treated gestationally with angiotensin 1-7 (Ang1-7, angiotensin II-derived vasodilator), losartan (AT1 receptor antagonist), pioglitazone (peroxisome proliferator-activated receptor gamma, PPARγ, agonist), or combined losartan/pioglitazone were instrumented with femoral indwelling catheters and challenged intravenously with a 5-mg/kg dose of lipopolysaccharides (LPS, 5 mg/kg). LPS caused significant decreases in blood pressure (BP) and spectral index of overall heart rate variability and increases in heart rate and left ventricular contractility (dP/dtmax). These effects were mostly reduced to similar magnitudes by individual drug therapies. In offspring born to Ang1-7-treated dams, the spectral index of cardiac sympathovagal balance showed elevated sympathetic dominance in response to LPS. Immunohistochemistry revealed that Ang1-7, but not losartan/pioglitazone, abolished the exaggerated increases in toll-like receptor 4 (TLR-4) expression caused by PE/LPS in heart tissues and neuronal circuits of brainstem rostral ventrolateral medulla (RVLM). By contrast, the losartan/pioglitazone regimen, but not Ang1-7, decreased and increased angiotensin converting enzyme (ACE) and ACE2 expression, respectively. Together, gestational fetal reprogramming of Ang II (depression) and Ang1-7 (activation) arms of RAS effectively counterbalance worsened endotoxic cardiovascular and inflammatory profiles in adult male offspring of PE rats.

Resin-based dental pulp capping restoration enclosing silica and portlandite nanoparticles from natural resources.

Natural-based materials represent green choices for biomedical applications. In this study, resin pulp capping restoration enclosing strengthening silica and bioactive portlandite nanofillers were prepared from industrial wastes. Silica nanoparticles were isolated from rice husk by heat treatment, followed by dissolution/precipitation treatment. Portlandite nanoparticles were prepared by calcination of carbonated lime waste followed by ultrasonic treatment. Both were characterized using x-ray diffraction, energy dispersive x-ray, and transmission electron microscopy. For preparing pulp capping restoration, silica (after silanization) and/or portlandite nanoparticles were mixed with 40/60 weight ratio of bisphenol A-glycidyl methacrylate and triethylene glycol dimethacrylate. Groups A, B, and C enclosing 50 wt.% silica, 25 wt.% silica + 25 wt.% portlandite, and 50 wt.% portlandite, respectively, were prepared. All groups underwent microhardness, compressive strength, calcium release, pH, and apatite forming ability inspection in comparison to mineral trioxide aggregate (MTA) positive control. In comparison to MTA, all experimental groups showed significantly higher compressive strength, group B showed comparable microhardness, and group C showed significantly higher calcium release. Groups B and C showed prominent hydroxyapatite formation. Thus, the preparation of economic, silica-fortified, bioactive pulp capping material from under-utilized agricultural residues (rice husk) and zero-value industrial waste (carbonated lime from sugar industry) could be achieved.

Non-Invasive Brain Sensing Technologies for Modulation of Neurological Disorders.

The non-invasive brain sensing modulation technology field is experiencing rapid development, with new techniques constantly emerging. This study delves into the field of non-invasive brain neuromodulation, a safer and potentially effective approach for treating a spectrum of neurological and psychiatric disorders. Unlike traditional deep brain stimulation (DBS) surgery, non-invasive techniques employ ultrasound, electrical currents, and electromagnetic field stimulation to stimulate the brain from outside the skull, thereby eliminating surgery risks and enhancing patient comfort. This study explores the mechanisms of various modalities, including transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), highlighting their potential to address chronic pain, anxiety, Parkinson's disease, and depression. We also probe into the concept of closed-loop neuromodulation, which personalizes stimulation based on real-time brain activity. While we acknowledge the limitations of current technologies, our study concludes by proposing future research avenues to advance this rapidly evolving field with its immense potential to revolutionize neurological and psychiatric care and lay the foundation for the continuing advancement of innovative non-invasive brain sensing technologies.

Exploring the use of clay pots as sustainable storage containers to improve water quality.

BACKGROUND: Currently, tap water consumption is not highly preferred in Egypt and around the world. People prefer to consume bottled water because they believe that it is much safer and tastes better than tap water. Unfortunately, this preference can create an economic burden for many people, especially in developing countries. Clay pots can be used to provide cool, alkaline drinking water because of their porous micro-texture, which traps pollutants. This study aimed to investigate the use of clay pots to store tap water and its impact on the requirements for drinking water quality. This is done with the intent to decrease the need for bottled water as a means of offering a more sustainable and economical option. METHODS: In this study, the efficiency of clay pots as sustainable storage containers for drinking water was tested by measuring physicochemical parameters (pH, TDS, EC, turbidity, DO, ammonia, chloride, total hardness, Ca hardness, Mg hardness, chlorine, Zn, and CaCO3) and biological parameters (TPC and Legionella). RESULTS: After 7 days of storage, the quality of the water stored in clay pots met the standards set by the Egyptian law with a significant difference (p < 0.05) before and after the storage of water It was found that the dissolved oxygen increased from 6.17 ppm to 7.52 ppm after 7 days. As for total hardness, it declined from 195 to 178 ppm. There was also a significant drop in terms of TDS from 338 to 275 ppm. Furthermore, clay pots effectively filtered out both total viable bacteria and Legionella. CONCLUSION: This study proved the efficiency of using these containers with respect to some indicator values for tap water and tank water analysis. Clay pots are an excellent, cost-effective, and sustainable alternative for storing water.

Suppression by central adenosine A3 receptors of the cholinergic defense against cardiovascular aberrations of sepsis: role of PI3K/MAPKs/NFκB signaling.

Introduction: Despite the established role of peripheral adenosine receptors in sepsis-induced organ dysfunction, little or no data is available on the interaction of central adenosine receptors with sepsis. The current study tested the hypothesis that central adenosine A3 receptors (A3ARs) modulate the cardiovascular aberrations and neuroinflammation triggered by sepsis and their counteraction by the cholinergic antiinflammatory pathway. Methods: Sepsis was induced by cecal ligation and puncture (CLP) in rats pre-instrumented with femoral and intracisternal (i.c.) catheters for hemodynamic monitoring and central drug administration, respectively. Results: The CLP-induced hypotension, reduction in overall heart rate variability (HRV) and sympathovagal imbalance towards parasympathetic predominance were abolished by i.v. nicotine (100 µg/kg) or i.c. VUF5574 (A3AR antagonist, 2 µg/rat). In addition, the selective A3AR agonist, 3-iodobenzyl-5'-N-methylcarboxamidoadenosine IB-MECA, 4 µg/rat, i.c.) exaggerated the hypotension and cardiac autonomic dysfunction induced by sepsis and opposed the favorable nicotine actions against these septic manifestations. Immunohistochemically, IB-MECA abolished the nicotine-mediated downregulation of NFκB and NOX2 expression in rostral ventrolateral medullary areas (RVLM) of brainstem of septic rats. The inhibitory actions of IB-MECA on nicotine responses disappeared after i.c. administration of PD98059 (MAPK-ERK inhibitor), SP600125 (MAPK-JNK inhibitor) or wortmannin (PI3K inhibitor). Moreover, infliximab (TNFα inhibitor) eliminated the IB-MECA-induced rises in RVLM-NFκB expression and falls in HRV, but not blood pressure. Conclusion: Central PI3K/MAPKs pathway mediates the A3AR counteraction of cholinergic defenses against cardiovascular and neuroinflammatory aberrations in sepsis.