Sorbate metal complexes as newer antibacterial, antibiofilm, and anticancer compounds.

BACKGROUND: The ineffectiveness of treatments for infections caused by biofilm-producing pathogens and human carcinoma presents considerable challenges for global public health organizations. To tackle this issue, our study focused on exploring the potential of synthesizing new complexes of Co(II), Cu(II), Ni(II), and Zn(II) with sorbic acid to enhance its antibacterial, antibiofilm, and anticancer properties. METHODS: Four novel complexes were synthesized as solid phases by reacting sorbic acid with Co(II), Cu(II), Ni(II), and Zn(II). These complexes were characterized by various technique, including infrared spectra, UV-Visible spectroscopy, proton nuclear magnetic resonance (1H NMR), and thermal analysis techniques, including thermogravimetry (TG). RESULTS: The data acquired from all investigated chemical characterization methods confirmed the chemical structure of the sorbate metal complexes. These complexes exhibited antibacterial and antibiofilm properties against both Gram-positive and Gram-negative bacteria. Furthermore, these complexes enhanced the antibacterial effects of commonly used antibiotics, such as gentamicin and imipenem, with fractional inhibitory concentration (FIC) indices ≤ 0.5. Notably, the Cu(II) complex displayed the most potent antibacterial and antibiofilm activities, with minimum inhibitory concentration (MIC) values of 312.5 µg/mL and 625.0 µg/mL for Bacillus cereus and Escherichia coli, respectively. Additionally, in vitro assays using the methyl thiazolyl tetrazolium (MTT) method showed inhibitory effects on the growth of the human colon carcinoma cell line (HCT-116 cells) following treatment with the investigated metal complexes. The IC50 values for Co(II), Cu(II), Zn(II), and Ni(II) were 3230 µg/mL, 2110 µg/mL, 3730 µg/mL, and 2240 µg/mL, respectively. CONCLUSION: Our findings offer potential for pharmaceutical companies to explore the development of novel combinations involving traditional antibiotics or anticancer drugs with sorbate copper complex.

Boosting the Anti-Helicobacter Efficacy of Azithromycin through Natural Compounds: Insights From In Vitro, In Vivo, Histopathological, and Molecular Docking Investigations.

BACKGROUND: Antimicrobial-resistant Helicobacter pylori (H. pylori) poses a significant public health concern, especially given the limited therapeutic options for azithromycin-resistant strains. Hence, there is a necessity for new studies to reconsider the use of azithromycin, which has diminished in effectiveness against numerous strains. Thus, we aimed to augment azithromycin's anti-Helicobacter properties by combining it with curcumin in different formulations, including curcumin in clove oil, curcumin nano-gold emulsion, and curcumin nanoemulsion. METHODS: The antimicrobial activities of the investigated compounds, both individually and in combination with other anti-Helicobacter drugs, were evaluated. Their antibiofilm and anti-virulence properties were assessed using both phenotypic and genotypic methods, alongside molecular docking studies. Our findings were further validated through mouse protection assays and histopathological analysis. RESULTS: We observed high anti-Helicobacter activities of curcumin, especially curcumin nanoemulsion. A synergistic effect was detected between curcumin nanoemulsion and azithromycin with fraction inhibitory concentration index (FICI) values <0.5. The curcumin nanoemulsion was the most active anti-biofilm and anti-virulence compound among the examined substances. The biofilm-correlated virulence genes (babA and hopQ) and ureA genes were downregulated (fold change <1) post-treatment with curcumin nanoemulsion. On the protein level, the anti-virulence activities of curcumin nanoemulsion were documented based on molecular docking studies. These findings aligned with histopathological scoring of challenge mice, affirming the superior efficacy of curcumin nanoemulsion/azithromycin combination. CONCLUSION: The anti-Helicobacter activities of all curcumin physical forms pose significant challenges due to their higher  minimum inhibitory concentration (MIC) values exceeding the maximum permissible level. However, using curcumin nanoemulsion at sub-MIC levels could enhance the anti-Helicobacter activity of azithromycin and exhibit anti-virulence properties, thereby improving patient outcomes and addressing resistant pathogens. Therefore, more extensive studies are necessary to assess the safety of incorporating curcumin nanoemulsion into H. pylori treatment.

Design, spectroscopic characterizations, and biological investigation of oxospiro[chromine-4,3-indolene]-based compounds as promising antiproliferative EGFR inhibitors and antimicrobial agents.

Utilizing microwave heating and an aqueous saturated solution of K2CO3 as a catalyst, a rapidone-pot synthesis of oxospiro[chromene-4.3-indoline] derivatives was produced in high yields. The experimental results confirmed that the saturated solution of K2CO3 gives outstanding yield to dangerous metals and strong bases during investigations into high-performance catalysts. The used catalyst is green, affordable, incredibly mild, and widely accessible. However, it generates samples, reduces the amount of byproducts, and is expected to be used in industrial-scale heterocyclic derivatives. New oxospiro[chromene-4.3-indoline] derivatives have been created from various isatin by condensing with various phenols. The biological activities results showed that when compared to erlotinib, the derivatives 3b, 4b, 5b, and 6b were the most effective analogues on A549, MCF-7, HepG-2, and HCT-116 cells, with an IC50 range of 3.32 to 11.88 µM. In A549 cells, compounds 3b, 4b, 5b, and 6b induced apoptosis, as shown by the up-regulation of Bax, the up-regulation of Bcl-2, and the stimulation of caspase-3 and -9. With IC50 value of 0.19 ± 0.09, compound3b was demonstrated to be the most effective against EGFRWT. Compounds 4b and 6b have good antibacterial activity toward Staphylococcus aureus, comparable to ciprofloxacin, and about half as much activity as ampicillin, according to the MIC value. Compound 6b's MIC is about 25% lower than clotrimazole drug. The in silico molecular docking outcomes of compounds 3b, 4b, 5b, and 6b in the EGFR active site depicted their ability to adopt essential binding interactions compared to the reference Erlotinib. Moreover, the investigation of the physicochemical properties of the most promising dual acting antiproliferative and antimicrobial compounds 4b and 6b through the egg-boiled method illustrated acceptable lipophilicity, GIT absorption, and blood-brain barrier penetration characteristics.

Guanidine dicycloamine-based analogs: green chemistry synthesis, biological investigation, and molecular docking studies as promising antibacterial and antiglycation leads.

Dicyandiamide (DCD) reacted with amino acids 1a-f to produce biguanides 2 and 4 and guanidine pyrazolones 3, 5, 6, 7, and 8, according to the reaction. DCD exhibited the following reactions: imidodicarbonimidicdiamide 9, diazocan-2-ylguanidine 10, methyl biguanidylthion 11, N-carbamothioylimidodicarbonimidicdiamide 12, 2-guanidinebenzoimidazole 13a, 2-guanidinylbenzoxazole 13b, and 2-guanidinylbenzothiazol 13c. These reactions were triggered by 6-amino caproic acid, thioacetamide, thiourea, o-aminophenol, o-aminothiophenol, and anthranilic acid, respectively. Compound 2 had the least antimicrobial activity, while compound 13c demonstrated the most antibacterial impact against all bacterial strains. Furthermore, in terms of antiglycation efficacy (AGEs), 12, 11, and 7 were the most effective AGE cross-linking inhibitors. Eight and ten, which showed a considerable inhibition on cross-linking AGEs, come next. Compounds 4 and 6 on the other hand have shown the least suppression of AGE production. The most promising antiglycation scaffolds 8, 11, and 12 in the Human serum albumin (HAS) active site were shown to be able to adopt crucial binding interactions with important amino acids based on the results of in silico molecular docking. The most promising antiglycation compounds 8, 11, and 12 were also shown to have better hydrophilicity, acceptable lipophilicity, gastrointestinal tract absorption (GIT), and blood-brain barrier penetration qualities when their physicochemical properties were examined using the egg-boiled method.

Anti-leishmanial activities of Olea europaea subsp. laperrinei extracts.

Leishmaniasis is an infectious disease that is often fatal in affected patients and represents a major public health problem. At present, no vaccine is available, and the drug treatments used are costly, long, and have numerous side effects, they also present variable effectiveness, frequent relapses, and a more and more marked resistance towards the parasites. Thus, new therapeutic strategies are urgently needed, and they are mainly based on the research of active natural products. The objective of our study is the chemical characterization and the quantification of the polyphenol contents contained in the EAF and EAT extracts of the Laperrine olive tree and the evaluation of their antileishmania effect against Leishmania infantum. The quantification of polyphenols, flavonoids and total tannins shows a higher content in the leaf extract. We find respectively 776.76±30.64 mg gallic acid equivalent/g DR; 114.35±14.12 mg quercetin equivalent/g DR and 214.89±.17 mg tannic acid equivalent/g DR.The chemical characterization of Olea europaea subsp. laperrinei extracts show the presence of numerous antileishmanial biomolecules such as oleuropein, hydroxytyrosol, rutin, gallic acid, cafeic acid, rosmarinic acid, and quercetin.In this context, we are testing the in vitro leishmanicidal effect of Laperrine olive tree extracts. The results obtained are promising and highlight the effectiveness of the tested extracts against the promastigote form of Leishmania infantum. Indeed, the LD50 is obtained with the leaf extract at a concentration of 7.52±2.71 µl/ml.

Enhanced Wound Healing Potential of Spirulina platensis Nanophytosomes: Metabolomic Profiling, Molecular Networking, and Modulation of HMGB-1 in an Excisional Wound Rat Model.

Excisional wounds are considered one of the most common physical injuries. This study aims to test the effect of a nanophytosomal formulation loaded with a dried hydroalcoholic extract of S. platensis on promoting excisional wound healing. The Spirulina platensis nanophytosomal formulation (SPNP) containing 100 mg PC and 50 mg CH exhibited optimum physicochemical characteristics regarding particle size (598.40 ± 9.68 nm), zeta potential (-19.8 ± 0.49 mV), entrapment efficiency (62.76 ± 1.75%), and Q6h (74.00 ± 1.90%). It was selected to prepare an HPMC gel (SPNP-gel). Through metabolomic profiling of the algal extract, thirteen compounds were identified. Molecular docking of the identified compounds on the active site of the HMGB-1 protein revealed that 12,13-DiHome had the highest docking score of -7.130 kcal/mol. SPNP-gel showed higher wound closure potential and enhanced histopathological alterations as compared to standard (MEBO® ointment) and S. platensis gel in wounded Sprague-Dawley rats. Collectively, NPS promoted the wound healing process by enhancing the autophagy process (LC3B/Beclin-1) and the NRF-2/HO-1antioxidant pathway and halting the inflammatory (TNF-, NF-κB, TlR-4 and VEGF), apoptotic processes (AIF, Caspase-3), and the downregulation of HGMB-1 protein expression. The present study's findings suggest that the topical application of SPNP-gel possesses a potential therapeutic effect in excisional wound healing, chiefly by downregulating HGMB-1 protein expression.

Delayed seropositivity is associated with lower levels of SARS-CoV-2 antibody levels in patients with mild to moderate COVID-19.

BACKGROUND: Patients with COVID-19 can develop a range of immune responses, including variations in the onset and magnitude of antibody formation. The aim of this study was to investigate whether SARS-CoV-2 antibody levels vary in patients with mild to moderate COVID-19 in relation to the onset (days) of their post-symptom seropositivity and to explore host factors that may affect antibody production METHODS: This was a prospective, multiple measurements study involving 92 PCR-confirmed patients with mild to moderate COVID-19. Antibody testing for anti-nucleocapsid (anti-NP) and spike proteins (anti-S) was performed using ELISA tests. Serum samples were collected over a period of 55 days from symptom onset of COVID-19 infection, and repeated as necessary until they turned positive. RESULTS: No significant differences were found between the positivity rates of anti-S or anti-NP regarding any clinical symptom (p > 0.05). The majority of patients who tested positive for anti-NP and anti-S showed early seropositivity (within 15 days of symptom onset) (75.9% for anti-NP and 82.6% for anti-S). Younger patients, those without chronic diseases, and non-healthcare workers had the highest percentage of seroconversion after day 35 post-symptom onset (p = 0.002, 0.028, and 0.036, respectively), while older patients and those with chronic diseases had earlier seropositivity and higher anti-NP levels (p = 0.003 and 0.06, respectively). Significantly higher anti-S ratios were found among older (p = 0.004), male (p = 0.015), and anemic patients (p = 0.02). A significant correlation was found between both antibodies (p = 0.001). At the end of the study, the cumulative seroconversion rate for both antibodies was almost 99%. CONCLUSIONS: Some COVID-19 patients may exhibit delayed and weak immune responses, while elderly, anemic patients and those with chronic diseases may show earlier and higher antibody responses.

Comparative efficacy of intralesional 5 flurouracil and intralesional triamcinolone acetonide in localized plaque psoriasis.

Psoriasis is a papulosquamous disorder that causes significant social and psychological trauma to the patient. It is characterized by the presence of erythematous, indurated plaques covered with silvery-white scales. Despite the availability of several systemic agents that have been approved for the treatment of psoriasis, usually there are some residual lesions and there is a need to treat them for cosmetic reasons or symptomatic control. 1. Treatment of resistant localized psoriatic plaques or residuals after systemic treatment. 2. Recently, some intralesional agents have been used successfully for the treatment of psoriatic plaques as 5-FU, methotrexate, and botulinum toxin type-A, and nearly for four decades, no study focused on the effect of intralesional corticosteroids in the treatment of these psoriatic plaques. We decided to highlight their role and compare intralesional Triamcinolone to intralesional 5-FU regarding efficacy and safety in the treatment of plaque psoriasis. This study included 24 patients with localized plaque psoriasis. Each patient was treated by split-body therapy where one psoriatic plaque was treated with intralesional 5FU and another plaque with intralesional TAC. A total of three injections were given at 2-week intervals and follow up was regularly every 2 weeks up to 12 weeks. There was a statistically significant difference between both groups (p = 0.008) as the response rate on 5-FU side was 12.5% with no response, 29.2% with a moderate response, 41.7% with an excellent response, and 16.7% with a complete clearance, while on the TAC side it was16.7% with a moderate response, 20.8% with an excellent response and 62.5% with a complete clearance. Hyperpigmentation was the most irritating side effect of 5-FU that occurred. Pain, during and after injection, was greater in 5-FU group. Hypopigmentation and atrophy only occurred in TAC group in some patients but it seems to be reversible and not disfiguring. 1-Intralesional TAC injection may have more efficacy and less side effects than 5-FU injection in the treatment of localized plaque psoriasis. Hyperpigmentation and pain were the most irritating side effects of 5-FU 2-Intralesional TAC can be effective in the treatment of localized psoriatic plaques with minimal side effects, especially in patients not suitable for systemic agents.

Metallo-Beta-Lactamase Producing Pseudomonas aeruginosa in a Healthcare Setting in Alexandria, Egypt.

Pseudomonas aeruginosa has emerged as a major healthcare associated pathogen that creates a serious public health disaster in both developing and developed countries. In this work we aimed at studying the occurrence of metallo-beta-lactamase (MBL) producing P. aeruginosa in a healthcare setting in Alexandria, Egypt. This cross sectional study included 1583 clinical samples that were collected from patients admitted to Alexandria University Students' Hospital. P. aeruginosa isolates were identified using standard microbiological methods and were tested for their antimicrobial susceptibility patterns using single disc diffusion method according to the Clinical and Laboratory Standards Institute recommendations. Thirty P. aeruginosa isolates were randomly selected and tested for their MBL production by both phenotypic and genotypic methods. Diagnostic Epsilometer test was done to detect metallo-beta-lactamase enzyme producers and polymerase chain reaction test was done to detect imipenemase (IMP), Verona integron-encoded (VIM) and Sao Paulo metallo-beta-lactamase (IMP) encoding genes. Of the 1583 clinical samples, 175 (11.3%) P. aeruginosa isolates were identified. All the 30 (100%) selected P. aeruginosa isolates that were tested for MBL production by Epsilometer test were found to be positive; where 19 (63.3%) revealed blaSPM gene and 11 (36.7%) had blaIMP gene. blaVIM gene was not detected in any of the tested isolates. Isolates of MBL producing P. aeruginosa were highly susceptible to polymyxin B 26 (86.7%) and highly resistant to amikacin 26 (86.7%). MBL producers were detected phenotypically by Epsilometer test in both carbapenem susceptible and resistant P. aeruginosa isolates. blaSPM was the most commonly detected MBL gene in P. aeruginosa isolates.

The role of current synthetic and possible plant and marine phytochemical compounds in the treatment of acne.

Acne is a long-standing skin condition characterized by plugged hair follicles due to the accumulation of dead skin cells, sebum, and Propionibacterium acnes (P. acnes) bacteria, causing inflammation, and the formation of pimples or lesions. Acne was recognized in the ancient times by the ancient Egyptians, Greeks, and Romans. Since ancient times, folk medicine from different cultures have comprised herbal and natural products for the treatment of acne. Current acne medications include antibiotics, keratolytics, corticosteroids, in addition to hormonal therapy for women. However, these conventional drugs can cause some serious side effects. And therefore, seeking new safe treatment options from natural sources is essential. Plants can be a potential source of medicinal phytochemicals which can be pharmacologically active as antibacterial, antioxidant, anti-inflammatory, keratolytic and sebum-reducing. Organic acids, obtained from natural sources, are commonly used as keratolytics in dermatology and cosmetology. Most of the promising phytochemicals in acne treatment belong to terpenes, terpenoids, flavonoids, alkaloids, phenolic compounds, saponins, tannins, and essential oils. These can be extracted from leaves, bark, roots, rhizomes, seeds, and fruits of plants and may be incorporated in different dosage forms to facilitate their penetration through the skin. Additionally, medicinal compounds from marine sources can also contribute to acne treatment. This review will discuss the pathogenesis, types and consequences of acne, side effects of conventional treatment, current possible treatment options from natural sources obtained from research and folk medicine and possible applied dosage forms.

Multimodal modulation of hepatic ischemia/reperfusion-induced injury by phytochemical agents: A mechanistic evaluation of hepatoprotective potential and safety profiles.

BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is a clinically fundamental phenomenon that occurs through liver resection surgery, trauma, shock, and transplantation. AIMS OF THE REVIEW: This review article affords an expanded and comprehensive overview of various natural herbal ingredients that have demonstrated hepatoprotective effects against I/R injury through preclinical studies in animal models. MATERIALS AND METHODS: For the objective of this investigation, an extensive examination was carried out utilizing diverse scientific databases involving PubMed, Google Scholar, Science Direct, Egyptian Knowledge Bank (EKB), and Research Gate. The investigation was conducted based on specific identifiable terms, such as hepatic ischemia/reperfusion injury, liver resection and transplantation, cytokines, inflammation, NF-kB, interleukins, herbs, plants, natural ingredients, phenolic extract, and aqueous extract. RESULTS: Bioactive ingredients derived from ginseng, curcumin, resveratrol, epigallocatechin gallate, quercetin, lycopene, punicalagin, crocin, celastrol, andrographolide, silymarin, and others and their effects on hepatic IRI were discussed. The specific mechanisms of action, signaling pathways, and clinical relevance for attenuation of liver enzymes, cytokine production, immune cell infiltration, oxidative damage, and cell death signaling in rodent studies are analyzed in depth. Their complex molecular actions involve modulation of pathways like TLR4, NF-κB, Nrf2, Bcl-2 family proteins, and others. CONCLUSION: The natural ingredients have promising values in the protection and treatment of various chronic aggressive clinical conditions, and that need to be evaluated on humans by clinical studies.

Memes Adoption in Basic Medical Science Education as a Successful Learning Model: A Mixed Method Quasi-Experimental Study.

Purpose: Basic medical sciences are of a solid abstract nature. Pharmacology is a challenging discipline delivered in all healthcare-related curricula with different aims and goals. Memes are one of aiding instructional designs proved to surge students' performance and satisfaction with the educational process. Apart from assessing medical students' and faculty's perception of meme use in pharmacology learning, the current study aimed to explore the criteria of preferences and factors associated with successful memes' adoption in this discipline as one of the most challenging basic medical sciences. Methods: A biphasic study was conducted among second-year undergraduate medical students and faculty members. The study involved assessing the perceptions of staff and students, and thematic content analysis was performed on the narrative responses of the participants to explore factors contributing to the success of learning memes. Additionally, students' performance was also analyzed. Results: The use of memes in pharmacology was well perceived by medical students, with a mean satisfaction rating of 4.5/5 for high-achieving students and 4.33 for low-achieving students. Memes were associated with a performance surge (p = 0.022). Six themes emerged as criteria for a successful learning experience of meme use: previous scientific background on the meme topic, scenario context of the meme, learning concepts tackled by memes, the simplicity of meme's message, the relevance of meme's message to practice, and the modality of meme's use in the topic of education. Regarding the perception of meme use in pharmacology learning, four themes emerged: the mode and engagement of learning experience mode, the feasibility of meme use in pharmacology learning, students' attitudes towards further meme inclusion in their study, and the perceived impact of memes on students' cognitive skills. Conclusion: The use of memes in pharmacology yields positive learning outcomes. A careful selection of memes is required to ensure a successful learning experience.

Wound Healing Efficacy of Cucurbitaceae Seed Oils in Rats: Comprehensive Phytochemical, Pharmacological, and Histological Studies Tackling AGE/RAGE and Nrf2/Ho-1 Cue.

The Cucurbitaceae family includes several edible species that are consumed globally as fruits and vegetables. These species produce high volumes of seeds that are often discarded as waste. In this study, we investigate the chemical composition and biological activity of three seed oils from Cucurbitaceae plants, namely, cantaloupe, honeydew, and zucchini, in comparison to the widely used pumpkin seed oil for their ability to enhance and accelerate wound healing in rats. Our results showed that honeydew seed oil (HSO) was effective in accelerating wound closure and enhancing tissue repair, as indicated by macroscopic, histological, and biochemical analyses, as compared with pumpkin seed oil (PSO). This effect was mediated by down-regulation of the advanced glycation end products (AGE) and its receptor (RAGE) cue, activating the cytoprotective enzymes nuclear factor erythroid 2 (Nrf2) and heme oxygenase-1 (HO-1), suppressing the inflammatory mediators tumor necrosis factor (TNF)-α, nuclear factor kappa B (NF-κB), and nod-like receptor protein 3 (NLRP3), and reducing the levels of the skin integral signaling protein connexin (CX)-43. Furthermore, immunohistochemical staining for epidermal growth factor (EGF) showed the lowest expression in the skin after treatment with HSO, indicating a well-organized and complete healing process. Other seed oils from cantaloupe and zucchini exhibited favorable activity when compared with untreated rats; however, their efficacy was comparatively lower than that of PSO and HSO. Gas chromatographic analysis of the derivatized oils warranted the superior activity of HSO to its high nutraceutical content of linoleic acid, which represented 65.9% of the fatty acid content. This study's findings validate the use of honeydew seeds as a wound-healing fixed oil and encourage further investigation into the potential of Cucurbitaceae seeds as sources of medicinally valuable plant oils.

Pinocembrin's protective effect against acute pancreatitis in a rat model: The correlation between TLR4/NF-κB/NLRP3 and miR-34a-5p/SIRT1/Nrf2/HO-1 pathways.

BACKGROUND: Acute pancreatitis (APS) is a prevalent acute pancreatic inflammation, where oxidative stress, inflammatory signaling pathways, and apoptosis activation contribute to pancreatic injury. METHODS: Pinocembrin, the predominant flavonoid in propolis, was explored for its likely shielding effect against APS provoked by two intraperitoneal doses of L-arginine (250 mg / 100 g) in a rat model. RESULTS: Pinocembrin ameliorated the histological and immunohistochemical changes in pancreatic tissues and lowered the activities of pancreatic amylase and lipase that were markedly elevated with L-arginine administration. Moreover, pinocembrin reinstated the oxidant/antioxidant equilibrium, which was perturbed by L-arginine, and boosted the pancreatic levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Pinocembrin markedly reduced the elevation in serum C-reactive protein (CRP) level induced by L-arginine. Additionally, it decreased the expression of high motility group box protein 1 (HMGB1), toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and NOD-like receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome in the pancreas. Furthermore, it also reduced myeloperoxidase (MPO) activity. Pinocembrin markedly downregulated miR-34a-5p expression and upregulated the protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) and Sirtuin 1 (SIRT1) and the gene expression level of the inhibitor protein of NF-κB (IκB-α), along with normalizing the Bax/Bcl-2 ratio. CONCLUSIONS: Pinocembrin notably improved L-arginine-induced APS by its antioxidant, anti-inflammatory, and anti-apoptotic activities. Pinocembrin exhibited a protective role in APS by suppressing inflammatory signaling via the TLR4/NF-κB/NLRP3 pathway and enhancing cytoprotective signaling via the miR-34a-5p/SIRT1/Nrf2/HO-1 pathway.

Alirocumab boosts antioxidant status and halts inflammation in rat model of sepsis-induced nephrotoxicity via modulation of Nrf2/HO-1, PCSK9/HMGB1/NF-ᴋB/NLRP3 and Fractalkine/CX3CR1 hubs.

Acute kidney injury (AKI) is a devastating consequence of sepsis, accompanied by high mortality rates. It was suggested that inflammatory pathways are closely linked to the pathogenesis of lipopolysaccharide (LPS)-induced AKI. Inflammatory signaling, including PCSK9, HMGB1/RAGE/TLR4/MYD88/NF-κB, NLRP3/caspase-1 and Fractalkine/CX3CR1 are considered major forerunners in this link. Alirocumab, PCSK9 inhibitor, with remarkable anti-inflammatory features. Accordingly, this study aimed to elucidate the antibacterial effect of alirocumab against E. coli in vitro. Additionally, evaluation of the potential nephroprotective effects of alirocumab against LPS-induced AKI in rats, highlighting the potential underlying mechanisms involved in these beneficial actions. Thirty-six adult male Wistar rats were assorted into three groups (n=12). Group I; was a normal control group, whereas sepsis-mediated AKI was induced in groups II and III through single-dose intraperitoneal injection of LPS on day 16. In group III, animals were given alirocumab. The results revealed that LPS-induced AKI was mitigated by alirocumab, evidenced by amelioration in renal function tests (creatinine, cystatin C, KIM-1, and NGAL); oxidative stress biomarkers (Nrf2, HO-1, TAC, and MDA); apoptotic markers and renal histopathological findings. Besides, alirocumab pronouncedly hindered LPS-mediated inflammatory response, confirmed by diminishing HMGB1, TNF-α, IL-1ß, and caspase-1 contents; the gene expression of PCSK9, RAGE, NF-ᴋB and Fractalkine/CX3CR1, along with mRNA expression of TLR4, MYD88, and NLRP3. Regarding the antibacterial actions, results showed that alirocumab displayed potential anti-bacterial activity against pathogenic gram-negative E. coli. In conclusion, alirocumab elicited nephroprotective activities against LPS-induced AKI via modulation of Nrf2/HO-1, PCSK9, HMGB1/RAGE/TLR4/MYD88/NF-ᴋB/NLRP3/Caspase-1, Fractalkine/CX3R1 and apoptotic axes.

Bio-fabricated zinc oxide nanoparticles mediated by endophytic fungus Aspergillus sp. SA17 with antimicrobial and anticancer activities: in vitro supported by in silico studies.

Introduction: In recent years, the world's attention has been drawn to antimicrobial resistance (AMR) because to the frightening prospect of growing death rates. Nanomaterials are being investigated due to their potential in a wide range of technical and biological applications. Methods: The purpose of this study was to biosynthesis zinc oxide nanoparticles (ZnONPs) using Aspergillus sp. SA17 fungal extract, followed by characterization of the produced nanoparticles (NP) using electron microscopy (TEM and SEM), UV-analysis, X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FT-IR). Results and Discussion: The HR-TEM revealed spherical nanoparticles with an average size of 7.2 nm, and XRD validated the crystalline nature and crystal structure features of the generated ZnONPs, while the zeta potential was 18.16 mV, indicating that the particles' surfaces are positively charged. The FT-IR was also used to identify the biomolecules involved in the synthesis of ZnONPs. The antibacterial and anticancer properties of both the crude fungal extract and its nano-form against several microbial strains and cancer cell lines were also investigated. Inhibition zone diameters against pathogenic bacteria ranged from 3 to 13 mm, while IC50 values against cancer cell lines ranged from 17.65 to 84.55 M. Additionally, 33 compounds, including flavonoids, phenolic acids, coumarins, organic acids, anthraquinones, and lignans, were discovered through chemical profiling of the extract using UPLC-QTOF-MS/MS. Some molecules, such pomiferin and glabrol, may be useful for antibacterial purposes, according to in silico study, while daidzein 4'-sulfate showed promise as an anti-cancer metabolite.

Lipid nanoparticles of quercetin (QU-Lip) alleviated pancreatic microenvironment in diabetic male rats: The interplay between oxidative stress - unfolded protein response (UPR) - autophagy, and their regulatory miRNA.

BACKGROUND: Autophagy is a well-preserved mechanism essential in minimizing endoplasmic reticulum stress (ER)-related cell death. Defects in ß-cell autophagy have been linked to type 1 diabetes, particularly deficits in the secretion of insulin, boosting ER stress sensitivity and possibly promoting pancreatic ß-cell death. Quercetin (QU) is a potent antioxidant and anti-diabetic flavonoid with low bioavailability, and the precise mechanism of its anti-diabetic activity is still unknown. Aim This study aimed to design an improved bioavailable form of QU (liposomes) and examine the impact of its treatment on the alleviation of type 1 diabetes induced by STZ in rats. METHODS: Seventy SD rats were allocated into seven equal groups 10 rats of each: control, STZ, STZ + 3-MA, STZ + QU-Lip, and STZ + 3-MA + QU-Lip. Fasting blood glucose, insulin, c-peptide, serum IL-6, TNF-α, pancreatic oxidative stress, TRAF-6, autophagy, endoplasmic reticulum stress (ER stress) markers expression and their regulatory microRNA (miRNA) were performed. As well as, docking analysis for the quercetin, ER stress, and autophagy were done. Finally, the histopathological and immunohistochemical analysis were conducted. SIGNIFICANCE: QU-Lip significantly decreased glucose levels, oxidative, and inflammatory markers in the pancreas. It also significantly downregulated the expression of ER stress and upregulated autophagic-related markers. Furthermore, QU-Lip significantly ameliorated the expression of several MicroRNAs, which both control autophagy and ER stress signaling pathways. However, the improvement of STZ-diabetic rats was abolished upon combination with an autophagy inhibitor (3-MA). The findings suggest that QU-Lip has therapeutic promise in treating type 1 diabetes by modulating ER stress and autophagy via an epigenetic mechanism.

Interictal electrocardiographic and echocardiographic changes in patients with generalized tonic-clonic seizures.

Partial and generalized seizures often affect autonomic functions during seizures, and interictal and postictal periods. We investigated possible interictal electrocardiographic abnormalities in patients with generalized tonic-clonic seizures (GTCS), together with evaluating any structural heart changes by echocardiography in these patients in comparison with healthy controls. We studied 120 definite GTCS patients (76 males and 44 females) who are neither diabetic nor under any medical treatment, and 60 healthy controls with a mean age of 25.2 ± 9.3 and 27.3 ± 7.5 years; respectively. Resting systolic and diastolic arterial blood pressures were measured, and standard 12-lead electrocardiograms and a 2-dimensional echocardiographic examination were performed. In univariate analysis, GTCS patients (compared to controls) had significantly lower means of PR interval (147.2 ± 18.6 versus 153.8 ± 22.6 msec; P = 0.037), QT interval (362.8 ± 22.9 versus 379.9 ± 29.3 msec; P < 0.001), and QTc interval (425.5 ± 20.7 versus 441.6 ± 19.9 msec; P < 0.001) but significantly higher mean left atrial diameter (3.49 ± 0.64 versus 3.09 ± 0.45 cm; P < 0.001). After adjusting for age, gender, and body mass index in a multivariate adjusted logistic regression model, left atrial diameter (OR = 3.941 [1.739 - 8.932]) and QTc (OR = 0.924 [0.895 - 0.954]) were significantly and independently associated with GTCS. In conclusion, patients with epilepsy may be predisposed to disturbances of autonomic functions with subsequent cardiac arrhythmias due to the effects of recurrent seizures on cardiac microstructure. Further work is needed to stratify the risk of sudden unexplained cardiac death (SUDEP) on the basis of interictal autonomic parameters to improve prognosis.

A multi-class deep learning model for early lung cancer and chronic kidney disease detection using computed tomography images.

Lung cancer is a fatal disease caused by an abnormal proliferation of cells in the lungs. Similarly, chronic kidney disorders affect people worldwide and can lead to renal failure and impaired kidney function. Cyst development, kidney stones, and tumors are frequent diseases impairing kidney function. Since these conditions are generally asymptomatic, early, and accurate identification of lung cancer and renal conditions is necessary to prevent serious complications. Artificial Intelligence plays a vital role in the early detection of lethal diseases. In this paper, we proposed a modified Xception deep neural network-based computer-aided diagnosis model, consisting of transfer learning based image net weights of Xception model and a fine-tuned network for automatic lung and kidney computed tomography multi-class image classification. The proposed model obtained 99.39% accuracy, 99.33% precision, 98% recall, and 98.67% F1-score for lung cancer multi-class classification. Whereas, it attained 100% accuracy, F1 score, recall and precision for kidney disease multi-class classification. Also, the proposed modified Xception model outperformed the original Xception model and the existing methods. Hence, it can serve as a support tool to the radiologists and nephrologists for early detection of lung cancer and chronic kidney disease, respectively.

Evaluation of the Cariogenic and Anti-Cariogenic Potential of Human Colostrum and Colostrum-Derived Probiotics: Impact on S. mutans Growth, Biofilm Formation, and L. rhamnosus Growth.

Human colostrum (HC) is essential for oral health as it is rich in probiotics that could affect the growth of the cariogenic S. mutans and its biofilm formation; hindering dental caries in advance. In this study, HC was collected from 36 healthy mothers 1-3 days postpartum. The effect of HC on oral health was carried out by assessing the impact of HC and its derived probiotics' cell-free supernatants (CFS) on the growth of S. mutans (using modified well diffusion) and its biofilm formation (using microtiter plate assay). Moreover, the effect of whole HC on L. rhamnosus, a probiotic oral bacterium, was examined. Probiotics were isolated and identified phenotypically by API 50 CH carbohydrate fermentation and genotypically by 16S rRNA amplification. The in vitro study revealed that HC has cariogenic activity and is associated with biofilm formation. Biofilm strength was inversely proportional to HC dilution (p-value < 0.0001). Nevertheless, HC and colostrum-derived probiotics improve oral health by inhibiting the growth of caries-inducing S. mutans with lower inhibition to L. rhamnosus probiotics. The CFS of isolated probiotics reduced the biofilm formation via the cariogenic S. mutans. These results are not only promising for caries eradication, but they also highlight the importance of breastfeeding infants from their first hours to shape healthy oral microbiota, protecting them from various diseases including dental caries.