Tailoring neo/adjuvant systemic therapy in breast cancer: "The advent of a personalized approach"-The Breast-Gynecological and Immuno-Oncology International Cancer Conference (BGICC) consensus and recommendations.

BACKGROUND: The management of early breast cancer (BC) has witnessed an uprise in the use of neoadjuvant therapy and a remarkable reshaping of the systemic therapy postneoadjuvant treatment in the last few years, with the evolution of many controversial clinical situations that require consensus. METHODS: During the 14th Breast-Gynecological and Immuno-Oncology International Cancer Conference held in Egypt in 2022, a panel of 44 BC experts from 13 countries voted on statements concerning debatable challenges in the neo/adjuvant treatment setting. The recommendations were subsequently updated based on the most recent data emerging. A modified Delphi approach was used to develop this consensus. A consensus was achieved when ≥75% of voters selected an answer. RESULTS AND CONCLUSIONS: The consensus recommendations addressed different escalation and de-escalation strategies in the setting of neoadjuvant therapy for early BC. The recommendations recapitulate the available clinical evidence and expert opinion to individualize patient management and optimize therapy outcomes. Consensus was reached in 63% of the statements (52/83), and the rationale behind each statement was clarified.

Exploring chaos and bifurcation in a discrete prey-predator based on coupled logistic map.

This research paper investigates discrete predator-prey dynamics with two logistic maps. The study extensively examines various aspects of the system's behavior. Firstly, it thoroughly investigates the existence and stability of fixed points within the system. We explores the emergence of transcritical bifurcations, period-doubling bifurcations, and Neimark-Sacker bifurcations that arise from coexisting positive fixed points. By employing central bifurcation theory and bifurcation theory techniques. Chaotic behavior is analyzed using Marotto's approach. The OGY feedback control method is implemented to control chaos. Theoretical findings are validated through numerical simulations.

Single and combined toxicity of tadalafil (Cilais) and microplastic in Tilapia fish (Oreochromis niloticus).

The joint impact of tadalafil (Cilais) as a pharmaceutical residue and microplastics on fish is not well comprehended. The current study examined haematological, biochemical, and antioxidant parameters, along with immunohistochemical and histological indications in tilapia (Oreochromis niloticus) after being exposed to tadalafil, polyethylene microplastics (PE-MPs), and their mixtures for 15 days. The fish were distributed into 1st group control group (The fish was maintained in untreated water without any supplements); 2nd group exposed to 10 mg/L PE-MPs;3rd group exposed to 20 mg/l tadalafil (Cilais); 4th group exposed to 20 mg/l tadalafil (Cilais) + 10 mg/LPE-MPs (in triplicate). The levels of creatinine, uric acid, glucose, AST, ALT, and albumin in fish treated with tadalafil alone or in combination with PE-MPs were significantly higher than those in the control group. Fish exposed to PE-MPs, tadalafil, and tadalafil plus PE-MPs showed significantly lower levels of RBCs, Hb, Ht, neutrophils, and lymphocytes compared to the control group. Serum levels of total antioxidant capacity and reduced glutathione (GSH) were notably lowered in fish groups subjected to PE-MPs, tadalafil, and tadalafil + PE-MPs combinations in comparison to the control group. Malondialdehyde (MDA) serum levels were notably elevated in fish groups subjected to PE-MPs, tadalafil, and tadalafil + PE-MPs combinations compared to the control group. The most severe impact was observed in the tadalafil + PE-MPs combination group. Interleukin-6 (IL-6) levels were significantly increased in liver tissues following exposure to both tadalafil and microplastics compared to tissues exposed to only one substance or the control group. Changes in the gills, liver, and renal tissues were seen following exposure to PE-MPs, tadalafil, and tadalafil + PE-MPs combination in comparison to the control group of fish. Ultimately, the mixture of tadalafil and PE-MPs resulted in the most detrimental outcomes. Tadalafil and PE-MPs exhibited showed greater adverse effects, likely due to tadalafil being absorbed onto PE-MPs.

Neurotoxic and cardiotoxic effects of pyrogallol on catfish (Clarias gariepinus).

Pyrogallol, a botanical hydrolysable tannin, has diverse medical and industrial applications. Its impact on aquatic ecosystems and fish health has been previously studied, revealing histopathological, immunological, biochemical, and haematological alterations in African catfish (Clarias gariepinus). In this study, the neurotoxic potential of pyrogallol was assessed through a 15-day exposure of catfish to concentrations of 1, 5, or 10 mg/L. Enzyme activities such as acetylcholinesterase (AchE), monoamine oxidase (MAO), aldehyde oxidase (AO), and nitric oxide (NO) were measured in serum and brain, along with histopathological examinations in the brain and heart. Pyrogallol exposure led to decreased AchE activity in the brain and serum, increased serum MAO activity, elevated AO in both brain and serum, and suppressed NO levels. Morphological abnormalities and dose-dependent pathological alterations were observed in the brain and heart, including neuropile deformities, shrunken Purkinje cells, cardiomyocyte degeneration, and increased collagen fibers. This suggests that pyrogallol induces adverse effects in fish.

Combination of metronomic capecitabine and letrozole in metastatic hormone receptor positive, HER2 negative breast cancer: a randomized phase II trial.

First line endocrine therapy is the gold standard for advanced estrogen receptor positive, human epidermal growth factor receptor 2 negative breast cancer. Adding CDK4/6 inhibitors has improved progression free survival. Metronomic Capecitabine has proven to be safe to combine with endocrine therapy with promising efficacy. We conducted a phase II randomized, open label, single centre clinical trial on patients with metastatic ER positive and HER 2 negative breast cancer. Eligible patients were randomized (1:1) to arm A: metronomic dose of capecitabine (500 mg/m2 BID) combined with letrozole (2.5 mg OD) or arm B: letrozole single agent. The primary endpoint was progression free survival. The study was terminated early due to poor accrual and 60 eligible patients out of the planned 204 were randomized. This clinical trial is registered on ClinicalTrials.gov (MD-127-2019, NCT04571437). Between February 2019 and April 2022, 60 patients were randomized. This is the first report of the study, after a median follow-up of 18.6 months. The median age at diagnosis was 47 years with only 41.7% of patients post-menopausal. Half of our patients had bone-only disease, 45% had visceral metastasis (liver and lung) and 63% presented with endocrine sensitive disease. The estimated median PFS for the whole population was 16.2 months. Median PFS for capecitabine arm was 17.7 months versus 14.6 months for letrozole alone (p = 0.078). Overall response rate was 70% for capecitabine/letrozole arm and 56.6% for letrozole only. Clinical benefit rate was 90% in the capecitabine/letrozole arm versus 73.3% in the letrozole arm. Overall survival data is still immature after this short follow up duration. Adverse event assessment showed acceptable all grade and high grade toxicity profile consistent with the established adverse events of both capecitabine and letrozole. Anaemia (28.3%) and hand & foot syndrome (43.8%) were significantly more common in the capecitabine/letrozole arm. Capecitabine combined with letrozole have showed a trend towards improvement in progression free survival with potential more benefit to certain sub-groups and the combination showed acceptable safety profile consistent with the established known safety profile of both letrozole and capecitabine.

Reproductive and endocrine-disrupting toxicity of pyrogallol in catfish (Clariasgariepinus).

Endocrine disruptors are synthetic or natural chemicals that can agonize/antagonize hormone receptors or can interfere with the production and secretion of hormones, leading to altered tissue histology and physiology. Pyrogallol is a contaminant widely distributed in aquatic environments that presents health risks to both humans and animals. However, the potential for endocrine disruption by pyrogallol, particularly in fish, are lacking. The purpose of this study was to shed light on how pyrogallol may affect hormone signalling, histopathology, and reproductive outcomes in African catfish Clarias gariepinus. To investigate this, African catfish were exposed to one sublethal concentration of pyrogallol at either 0, 1, 5 or 10 mg/L for 15 days. We then assessed the effects of pyrogallol on the thyroid gland as well as the reproductive system by measuring sex hormone, seminal quality, gonadal histopathology, and histochemistry. Thyroid stimulating hormone and thyroxine showed notable decreases in catfish, and triiodothyronine was decreased with 10 mg/L pyrogallol. Unlike luteinizing hormone, follicle-stimulating hormone was significantly reduced in fish following exposure to pyrogallol relative to controls. Testosterone was also decreased in fish following pyrogallol exposure, whereas 17ß-estradiol increased in catfish exposed to pyrogallol. Additionally, in response to pyrogallol toxicity, sperm quality indices, including count, spermatocrit, motility, and sperm viability were adversely affected in a concentration-dependent manner. Pyrogallol exposure also induced several changes in the gonad following exposure to 1, 5, or 10 mg/L. Deformed tubular structures, vacuolation, thickening of the basement membrane, hypertrophy of the seminiferous tubules, intense melanomacrophage localization, spermatozoa loss, and necrosis were all observed in the testes. In the ovary, atretic follicles, deteriorated mature oocytes, degenerated yolk globules, and an increase in perinucleolar oocytes were observed in catfish exposed to pyrogallol. These findings suggest that pyrogallol may act as endocrine disrupting substance in aquatic environments. Further research on the mechanisms by which pyrogallol impairs endocrine systems, particularly in fish, is recommended.

Fishmeal substitution by zooplankton or Daphnia magna biomass meals in the diet of Nile tilapia: Effects on growth, gut histological changes, bacterial abundance and stress tolerance.

Fishmeal substitution with sustainable feed sources is highly essential towards sustainable production. This study aimed to investigate the effects of substituting fishmeal (FM) with Daphnia magna biomass meal (DBM) or zooplankton biomass meal (ZBM) on growth performance, liver and intestinal histology, gut bacterial abundance and stress tolerance of Nile tilapia, Oreochromis niloticus, fry. Nile tilapia fry (0.23 ± 0.04 g) were randomly assigned to five groups of three replicates. The control diet comprised 300 g/kg FM, and the FM was substituted with DBM or ZBM at levels of 25% and 50% (DBM-25, DBM-50, ZBM-25 and ZBM-50 respectively) in the other experimental diets. The experiment lasted 56 days in 1.5 m3 concrete tanks. The results revealed that weight gain and feed conversion ratio (FCR) significantly (p ≤ 0.035 and 0.025 respectively) improved with a polynomial response with a peak at 25% ZBM and a linear increase with DBM up to 50% of FM. Histometric indices of the distal intestine showed improvements (p ≤ 0.001) in villus height, villus width, crypt depth and muscle thickness of fish fed DBM or ZBM compared to the control. In the meantime, there were no histological abnormalities in the liver sections. The replacement of FM with DBM or ZBM could modulated gut bacterial abundance, including total bacterial count, Escherichia coli, Bacillus subtilis, and Lactobacillus sp. The fish-fed DBM or ZBM-containing diets had higher (p ≤ 0.05) tolerances to salinity stress than the control group. In conclusion, DBM or ZBM could replace FM up to 50% and 25%, respectively with improved fish growth performance, FCR, gut histology and tolerance to salinity stress.

Synthesis of novel phthalazine-based derivatives with potent cytotoxicity against HCT-116 cells through apoptosis and VEGFR2 inhibition.

The parent ethyl 3-(4-benzyl-1-oxophthalazin-2(1H)-yl) propanoate (3) has 25 compounds. Their respective mono, dipeptides and hydrazones derivatives were produced by chemoselective N-alkylation via addition reaction of 4-benzylphthalazin-1(2H)-one (2) with ethyl acrylate and anhydrous potassium carbonate to give ethyl 3-(4-benzyl-1-oxophthalazin-2(1H)-yl) propanoate (3). The ester 3 was hydrazinolyzed to give the corresponding hydrazide 3-(4-benzyl-1-oxophthalazin-2(1H)-yl) propanehydrazide (5), then azide 6 coupled with amino acid ester hydrochloride and/or amines to afford several parent esters 8a-c, then a series of hydrazinolyzed reactions occurred to give corresponding hydrazides 9a-c. The hydrazide 9a was subjected to the azide coupling procedure, which resulted in the formation of various dipeptides. Subsequently, it was condensed with various aldehydes to yield hydrazone derivatives 13a-d. Interestingly, compounds 9c, 12b, and 13c exhibited potent cytotoxicity with IC50 values of 1.58, 0.32 and 0.64 µM compared to sorafenib (IC50 = 2.93 µM). Compound 12b exhibited potent VEGFR2 inhibition by 95.2% with an IC50 value of 17.8 µM compared to sorafenib (94.7% and IC50 of 32.1 µM). For apoptosis activity, 12b-treatment induced apoptosis in HCT-116 cells by 21.7-fold, arresting the cell proliferation at S-phase. Finally, it formed a good binding affinity towards VEGFR2 protein with a binding energy of -10.66 kcal mol-1, and it formed binding interactions with the key interactive amino acids.

The potential use of daphnia meal as substitute for fishmeal in diets of hybrid red tilapia affects growth performance, activities of digestive enzymes, antioxidant, immune status and intestinal histological parameters.

The current study aimed to evaluate growth performance, digestive enzyme activities, antioxidant status, nonspecific immune response and intestinal histological status of red tilapia fed Daphnia meal (DM) as a substitute for fishmeal (FM). Hybrid red tilapia (Oreochromis mossambicus × Oreochromis aureus) fry (0.54 ± 0.05 g fish-1) was allocated in nylon haba cages (100 fry m-3) for 2 weeks as an acclimation period. The fish were divided into five groups (three replicates each). The experimental diets were prepared by replacing FM with DM at concentrations of 25%, 50%, 75% and 100% respectively. The results indicated that fish fed increasing levels of DM (50%-75%) experienced high growth performance, feed utilisation and protein content. The activities of digestive enzymes were significantly increased in all groups fed DM diets compared to the control. The antioxidant balance was improved by decreasing the level of malondialdehyde and increased the total antioxidant capacity, catalase, superoxide dismutase and glutathione reductase activities in the liver of fish fed DM. The nonspecific immune response, including lysozyme, alkaline phosphatase activities and total protein level improved significantly with increasing FM substitution levels by DM in a dose-dependent manner. Histometric analysis of the intestinal wall revealed an increase in the villus length, crypts depth and goblet cells number in groups fed DM meal up to 50% substitution level compared to other treatments. It may be concluded from results of this feeding trial that in the aquaculture of hybrid tilapia, FM may be substituted with up to 50% DM without compromising intestinal health, growth performance and immune status of the fish.

New inorganic inhibitors derived from cefotaxime to enhance corrosion resistance of mild steel in 3% NaCl.

To overcome the threat of corrosion and its cost, a new Schiff base was prepared and utilized to synthesize inorganic inhibitors to enhance corrosion resistance and reduce current density. The Schiff base was obtained from the interaction of cefotaxime with acetylacetone, while 1H NMR and IR spectra were used to confirm the preparation. Moreover, FeIII, CoII, NiII and CuII metal salts were reacted with the Schiff base to give the corresponding complexes. Meanwhile, the non-ionic behavior of the observed complexes in solutions was proved from the conductance results. In addition, the octahedral geometry and the postulated structure of complexes were determined from CHNM%, IR spectroscopy, UV-visible spectra, and TGA analysis. Also, the energy of molecular orbitals (HOMO and LUMO) and other quantum mechanics parameters were calculated using the DFT method. The observed results indicated the reactivity of metal complexes and their ability to donate electrons more than the Schiff base. Furthermore, the corrosion rate of a steel sample under various concentrations of inhibitors was calculated by a potentiodynamic polarization test. The obtained data displayed that metal complexes declined the corrosion rate more than the Schiff base; therefore, the binding between the metal ion and the Schiff base improved the inhibition efficiency.

Saroglitazar mitigated NASH-associated hepatic injury in dexamethasone-treated rats via modulating autophagy, apoptosis, and necroptosis.

This study aimed to evaluate the possible ameliorative effects of saroglitazar (SAR) on aspects of hepatic injury in dexamethasone (DEX)-induced nonalcoholic steatohepatitis (NASH) in rats. Wistar rats received SAR (2 or 4 mg/kg/day, orally) or metformin (MET, 500 mg/kg/day, orally) for one week before and concurrently with DEX administration (8 mg/kg/day, i.p., for 6 days. Control and drug control groups received vehicle or the higher dose of SAR, respectively. At the end of the experiment, an oral glucose tolerance test (OGTT) was conducted, serum hepatic function parameters and lipid profile were assessed, and hepatic histological changes were evaluated. Moreover, hepatic p-Akt/Akt ratios, malondialdehyde (MDA) content, SREBP-1, FOXO1, LC3, cleaved caspase-3, and p-MLKL protein levels were determined. Furthermore, hepatic immunohistochemical expressions of FOXO1, caspase-3, Bcl-2, LC3, and P62 were examined. SAR (mainly at 4 mg/kg/day) significantly improved Area under the OGTT curve (P < 0.0001), hepatic function parameters, lipid profile, and hepatic histopathological features in DEX-administered rats. Moreover, SAR significantly attenuated DEX-induced increases in hepatic MDA content (P < 0.05), SREBP-1 levels (P < 0.0001), and nuclear FOXO1, caspase-3, LC3, P62, and p-MLKL protein expressions (P < 0.0001). Furthermore, SAR significantly enhanced hepatic p-Akt/Akt ratio and Bcl-2 protein expression in DEX-administered rats (P < 0.0001). The higher dose of SAR showed greater hepatoprotective effects compared to its corresponding lower dose and MET in most assessments, approaching levels similar to the control group. SAR mitigated hepatic injury associated with DEX-induced NASH in rats, suggesting it might be a potential hepatoprotective drug for patients with or at high risk of NASH.

Immunotoxicological, histopathological, and ultrastructural effects of waterborne pyrogallol exposure on African catfish (Clariasgariepinus).

Pyrogallol is a naturally occurring polyphenol derived from natural plants, such as Acer rubrum and Eucalyptus sp. The current study was designed to evaluated pyrogallol-mediated toxicity at sublethal levels (1, 5, and 10 mg/L), derived from 96 h-LC50 values previously determined for African catfish (Clarias gariepinus). Immunotoxicological indices, histological, histochemical, and ultrastructural alterations in C. gariepinus were evaluated following a 15-day pyrogallol exposure. Pyrogallol decreased immune parameters [lysozyme activity (LYZ), immunoglobulin M (IgM), and phagocytic activity] and increased pro-inflammatory cytokines, interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) in the serum of C. gariepinus. In addition, histopathology analysis demonstrated that exposure to pyrogallol induced injury in the liver and spleen of fish. Cellular changes in the liver include hepatocyte hydropic degeneration, melanomacrophage, vacuolated hepatocytes, congested blood, severe structural deformation, and hemorrhage. In the spleen, ellipsoid structures, melanomacrophage centers, and infiltration of inflammatory cells were evident. Together, a high frequency of histopathological lesions was scored in both the liver and spleen of C. gariepinus, which showed a dose-dependent relationship between pyrogallol exposure and histopathological indices. Our data suggest that dysfunction in the immune system may be mediated by pyrogallol-induced changes in cytokines.

Oxidative stress, antioxidant defense responses, and histopathology: Biomarkers for monitoring exposure to pyrogallol in Clarias gariepinus.

Pyrogallol promotes free radicals leading to oxidative stress and toxicity. There are however a lack of studies on oxidative stress and the antioxidant system of fish following exposure to pyrogallol. This study measured oxidative stress markers, antioxidant responses, and histological changes in catfish exposed to pyrogallol. Fish were divided into one of four experimental groups: control only, or 1, 5 or 10 mg/L pyrogallol. After 15 days, glutathione-S-transferase in the serum was decreased in fish exposed to either 5 or 10 mg/L pyrogallol relative to controls while superoxide dismutase and total antioxidant capacity were decreased significantly in fish exposed to 1, 5, or 10 mg/L pyrogallol. Conversely, catalase was increased in serum of fish exposed to 1, 5, or 10 mg/L pyrogallol compared to controls. The liver of fish treated with 1, 5, or 10 mg/L pyrogallol had significantly higher levels of oxidative stress markers (malondialdehyde, lipid peroxidation, hydroperoxide content, oxidised protein content, and DNA fragmentation %) that varied with concentration. Catfish exposed to either 1, 5, or 10 mg/L pyrogallol presented with notable histological alterations in the intestine, kidney, and muscles with prominent fibrosis, as intense deposition of collagen fibre was observed by Masson's trichrome staining. Overall, endpoints related to oxidative stress and antioxidant defence enzymes in fish may be early biomarkers of pyrogallol exposure and contamination in aquatic ecosystems. Additional studies should characterize oxidative stress indicators for their utility as biomarkers of effect.

Real-world treatment patterns and clinical outcomes in patients with stage III non-small cell lung cancer: results of KINDLE-Egypt cohort.

Background: Stage III non-small cell lung cancer (NSCLC) being highly heterogeneous requires multimodal therapeutic strategies for optimal management. We present findings on treatment patterns and their associated survival outcomes in patients with stage III NSCLC from the Egypt subset of the KINDLE global real-world study conducted across countries from Asia, Middle East, Africa, and Latin America. Method: Retrospective data from the Egypt subset (21 centers) of adult patients diagnosed with stage III NSCLC between January 2013 and December 2017 were analyzed. Descriptive and inferential statistics summarized treatment modalities, progression-free survival (PFS), and overall survival (OS). Results: Of 421 patients enrolled (median age: 59.0 years), 77.9% were males, 53.5% had stage IIIA disease, 60.8% had adenocarcinoma, 78.4% had an unresectable disease, and 81.5% had Eastern Cooperative Oncology Group performance status ⩽1. Overall, chemotherapy alone (40.4%) was predominantly used in the initial line, whereas definite radiotherapy was used in only 5.0% of patients. In resectable patients, chemotherapy plus surgery (33.8%), surgery alone (20.6%), or other surgery (20.6%) were the top three modalities used in initial line of treatment. Chemotherapy alone was most preferred (48.8%) in unresectable patients, followed by sequential chemoradiotherapy (CRT) (17.6%) and concurrent CRT (9.3%). The overall median PFS was 10.3 months [95% confidence interval (CI), 9.43-12.02], whereas the median OS was 18.5 months (95% CI, 16.46-21.88). Overall, female gender, adenocarcinoma histology, and radical therapy as surgery or CRT predicted significantly longer OS (all p < 0.05). Conclusion: KINDLE-Egypt cohort revealed wide heterogeneities in the treatment patterns of stage III NSCLC. Although deemed resectable, few patients did not undergo surgery, probably due to high smoking rates leading to poor lung function. Lower survival outcomes than other published real-world studies highlight the need for timely approval and availability of novel targeted and immunotherapies to enhance patient outcomes. Trial registration: NCT03725475.

Comparable Evaluation of Nutritional Benefits of Lactobacillus plantarum and Bacillus toyonensis Probiotic Supplementation on Growth, Feed Utilization, Health, and Fecal Microbiota in Pre-Weaning Male Calves.

This study was conducted to investigate the impact of probiotic supplementation using Lactobacillus plantarum DSA 20174 and/or Bacillus toyonensis ATCC 55050 on growth performance, blood parameters, hematological measures, and fecal microbiota in pre-weaning Holstein calves. Thirty-two four-day-old male calves with a similar genetic background, weighing an average of 38.27 ± 0.12 kg, were randomly assigned to four groups. The groups consisted of a control group (CON) without supplementation, a group receiving B. toyonensis (BT) at 3 × 109 cfu/calf/day, a group receiving L. plantarum (LP) at 1 × 1010 cfu/calf/day, and a group receiving a combination of LP and BT (LP + BT) at half the dosage for each. The study found that calves supplemented with LP and LP + BT experienced significant improvements in average daily gain and final body weight compared to the control group. The LP + BT group showed the most positive effects on TDMI, starter intake, and CP intake. RBC counts tended to be higher in the probiotic groups, with the LP + BT group having the highest values. The LP + BT group also had higher total protein, albumin, globulin, and hematocrit concentrations. All probiotic groups showed higher serum IgG concentrations. Probiotic supplementation led to increased total bacterial count and decreased levels of E. coli, salmonella, and clostridium. The LP + BT group had a significant decrease in coliform count, while both LP and LP + BT groups had increased Lactobacillus populations. In conclusion, LP + BT probiotic supplement showed the most beneficial effects on growth, feed efficiency, blood constituents, and modulation of fecal microbiota composition.

Potassium Spraying Preharvest and Nanocoating Postharvest Improve the Quality and Extend the Storage Period for Acid Lime (Citrus aurantifolia Swingle) Fruits.

Citrus fruits are one of the most abundant crops globally in more than 140 countries throughout the world. Acid lime (Citrus aurantifolia swingle) is one of the citrus fruits which popularly has rich nutritional and therapeutic features. The storage period is the important factor that affects the economic and quality properties of this fruit. This study aims to demonstrate the enhancing effect of preharvest spraying with potassium, in addition to the postharvest dipping of fruits in some edible coatings, on the quality and storability of acid lime fruits. Preharvest spraying with organic and mineral forms of potassium, namely, potassium thiosulfate 1.75 g/L (S) and potassium tartrate 2 g/L (T), were carried out at three different times, in May, June, and July. On the other hand, postharvest treatments were carried out via dipping fruits in different types of biopolymers (carboxymethyl cellulose (E2) and gum arabic (E3)) and carboxymethyl cellulose/gum arabic composite (E4) as well as nanocoating formulation based on both biopolymers and doped zinc oxide nanoparticles (ZnONPs) (E1), which were prepared via acid lime peel waste extract. Herein, the physiochemical and morphological characterizations confirmed that the nanocoating was prepared at the nanoscale and doped with green synthesis ZnONPs, with recorded sizes of around 80 and 20 nm, respectively. Preharvest spraying with potassium tartrate enhanced fruit traits (Spraying with potassium tartrate at pre-harvest and nanocoating dipping at post-harvest (TE1), spraying with potassium tartrate at pre-harvest and carboxy methyl cellulose dipping at post-harvest (TE2), spraying with potassium tartrate at pre-harvest and gum arabic dipping at post-harvest (TE3) and spraying with potassium tartrate at pre-harvest and carboxymethyl cellulose/gum arabic composite dipping at post-harvest (TE4)), followed by potassium thiosulfate (spraying with potassium thiosulfate at pre-harvest and nanocoating dipping at post-harvest (SE1), spraying with potassium thiosulfate at pre-harvest and carboxy methyl cellulose dipping at post-harvest (SE2), spraying with potassium thiosulfate at pre-harvest and gum arabic dipping at post-harvest (SE3) and spraying with potassium thiosulfate at pre-harvest and carboxymethyl cellulose/gum arabic dipping at post-harvest (SE4)), compared to control. For postharvest treatments, E1 improved fruit quality, followed by E2, E4, and E3, respectively. The integration between pre- and postharvest treatments showed a clear superiority of TE2, followed by TE4, SE1, and SE2, respectively.

Renoprotective Potency of Sitagliptin versus Pioglitazone in Type 2 Diabetic Patients: Impact on LncMIAT.

Background: Diabetes mellitus (DM) represents one of the most important reasons for chronic kidney diseases due to the high level of blood glucose that destructs blood vessels. Objective: The present study focused on investigating the protective impact of sitagliptin on kidney complication in type 2 diabetes mellitus (T2DM) patients in comparison to pioglitazone to examine which has the superior effect against the nephritic complication of DM. Methods: Eighty adult subjects were classified into four groups: control group, pioglitazone-treated T2DM patients (P group), sitagliptin-treated T2DM patients for less than one year (SL group), and sitagliptin-treated T2DM patients for more than one year (SM group). Blood samples were withdrawn from all subjects for analysis of neutrophil gelatinase-associated lipocalin (NGAL), vanin-1, kidney injury molecule-1 (KIM-1), glyoxalase-1 (Glo-1), methylglyoxal (MG), cystatin-C, and interleukin-18 (IL-18) using competitive ELISA kits. Also, long noncoding myocardial infarction associated transcript (lncMIAT) was measured in whole blood using qRT-PCR. Results: The present study revealed that the lncMIAT expression level was significantly higher in the P group as compared to the SL group, SM group, or healthy control group. Additionally, serum NGAL, vanin-1, KIM-1, Glo-1, MG, and cystatin-C were significantly higher in the P group and SL group as compared to the SM group and healthy control group. Conclusion: Sitagliptin protected the kidney through downregulation of lncMIAT besides amelioration of kidney injury marker levels, which was more preferable than in pioglitazone therapy.

Toxicity of co-exposure of microplastics and lead in African catfish (Clarias gariepinus).

Microplastics (MPs) are an emerging threat to freshwater ecosystems with several ecotoxicological ramifications for fish. Microplastics (MPs) can adsorb heavy metals on their surfaces and increase their availability to aquatic organisms. The combined impact of lead and microplastics on fish has only been studied seldom utilizing a variety of markers. The present study aimed to evaluate the hematological, biochemical, and inflammatory signals (cytokines), as well as antioxidant enzymes in African catfish (Clarias gariepinus) exposed to lead (Pb) and MPs individually and combined for 15 days (acute toxicity experiment). The fish were split into four groups, the first of which was the control group. The second group received exposure to 1 mg/L of lead nitrate [Pb(NO3)2]. The third group was given 100 mg/L of MPs. A solution containing 100 mg/L of MPs and 1 mg/L of lead nitrate [Pb(NO3)2] was administered to the fourth group (the combination group). According to the findings, when MPs and Pb were combined for 15 days, the red blood cells (RBCs), thrombocytes, and lymphocytes were significantly reduced in comparison to the control fish. When compared to the control fish, the fish exposed to MPs and Pb alone or together showed a significant rise in blood interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) cytokines. Both MPs and Pb exposure in catfish resulted in significant changes in the plasma electrolytes. The fish treated with MPs and Pb individually or in combination showed significant reduction in superoxide dismutase (SOD) and total antioxidant capacity (TAC) levels compared to the control group. The fish exposed to the combined action of MPs and Pb showed a considerable modification in all biochemical markers. The difference in the mean concentration of Pb (mg/L) between the fish exposed to Pb alone and the fish subjected to Pb and MPs combination was not statistically significant. In conclusion, according to this investigation, exposure to Pb caused an insignificant increase in Pb accumulation when MPs were present. However, co-exposure may result in anemia, cellular harm, extremely high levels of oxidative stress, and an inflammatory reaction.

Growth performance, digestive function, thyroid activity, and immunity of growing rabbits fed olive cake with or without Saccharomyces cerevisiae or citric acid.

The present study investigated the impact of dietary inclusion of olive cakes (OC) with or without Saccharomyces cerevisiae (SC) and citric acid (CA) on growth, digestive function, thyroid activity, antioxidant status, immunity, and intestinal architecture of growing rabbits. One hundred forty 35-day-old male New Zealand white rabbits were randomly assigned into seven experimental groups with five replicates each, as follows: control (CN), fed the basal diet; OC20 and OC25, fed diets with 20 and 25% OC; OS20 and OS25, fed diets containing 20 and 25% OC with S. cerevisiae at 5 g/kg diet; OA20 and OA25, fed diets supplemented with 20 and 25% OC with 1.0% citric acid. No differences in live body weight, feed intake, feed conversion ratio, and carcass traits were noticed among experimental groups, while body weight gain and carcass (%) were increased (P < 0.05) in OS20 compared to the control. Digestibility coefficients of all nutrients and activities of amylase, cellulose, and trypsin did not differ in treated groups compared to the control except for OS20, which recorded enhancement in nutrient digestibility. Plasma triiodothyronine and thyroxine were elevated (P < 0.05), while triglycerides and cholesterol were reduced (P < 0.05) in OS20 compared to CN. Plasma concentrations of immunoglobulin M and G and superoxide dismutase were increased in treated groups compared to the control. Dietary inclusion of SC and CA improved rabbits' intestinal health, as the cecal Lactobacillus count was increased, E. coli count was decreased, and villus height was elevated in SC- and CA-treated groups. In conclusion, dietary incorporation of SC or CA enhanced the nutritional value of OC and improved growth performance, nutrient digestibility, thyroid activity, antioxidative status, and gut health of growing rabbits.