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ABSTRACT The Samsum (black) ant, Pachycondyla sennaarensis (Formicidae; Hymenoptera) is widely distributed throughout sub-Saharan Africa, and it is also the most common species of the family in southern Arabia. Samsum ant is very invasive and economically damaging and has become a big problem in Saudi Arabia and other distribution countries due to their aggressive nature, severe stings, and harm to agriculture, natural ecosystems, and human health. The physicochemical properties and varied effects against insect pests make plant extracts a potential alternative in the development of pesticides. In this study, the Nerium oleander leaves extract toxicity effects against P. sennaarensis adults. Exposure of P. sennaarensis adult to the oleander leaf extracts produced 96.7% mortality in the insecticidal bioassay, especially at 40% concentration. The mortality % ranged from 3.3-96.7% after 48hrs. The mortality percentage of the Samsum ant adults decreased by increasing exposure periods. The mortality % was highly negatively correlated with exposure times (R= - 0.80 to - 0.94; P = 0001) at 40 to 10% concentrations, respectively. The overall results of the current study suggest that the leaf extract of N. oleander may possess potential insecticidal properties, which could potentially be employed in pest management. The GC-MS investigation uncovered that N. oleander leaf extracts numerous bioactive compounds associated with plant secondary metabolites with their retention time (RT), and peak area %. We conclude that the N. oleander leaf extracts have the potential to be useful in managing insect pests, particularly Samsum ants, but that they must be handled and applied with extreme caution.

The emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains, identified as resistant to at least isoniazid and rifampin, these two drugs form the backbone of the first line drug which is used for tuberculosis (TB) treatment, unresponsive has hampered TB control. As a result of the nearly universal calculation of with half a million new cases of MDR/first line drug TB per year, it is important to keep the database up to date awareness of the processes that contribute to the emergence of MDR Mtb. This resistance is produced for a variety of reasons, including genetic, microbiological factors, non-adherence to treatment by patients and/or failures in therapy administration by some referrer medical centre for TB. This review offers a detailed summary of genetic mechanisms that lead to resistant to first line drug therapy used in management of TB as well as up-to-date information on some new aspects lead to such problem. Keywords: Mycobacterium tuberculosis, first line drug, anti-TB treatment, World Health Organization, isoniazid and rifampin Citation: Hassan JS, Al-Tamimi BJ, Abdulrahman TR, Jamal QW. Resistance mechanisms to first line drug in Mycobacterium tuberculosis: A review. Iraqi JMS. 2022; 20(1): 35-43. doi: 10.22578/IJMS.20.1.5

Salmonella is approved as a common foodborne pathogen, causing major health problems throughout the world particularly in low‐ and middle‐income countries. Low-level fluoroquinolone resistance is conferred by both chromosomal and plasmid-encoded resistance, this research was carried out look into the occurrence rate of qnrA,qnrB and qnrS genes in Salmonella enterica serotype Typhi Cipr ofloxacin-resistant insulate from blood samples of patients with typhoid fever. Fifteen Salmonella enterica serotype Typhi isolated previously from patients with typhoid fever were included in this study. All bacterial isolates were confirmed to have ciprofloxacin resistant by VITEK 2 microbial identification system; after plasmid DNA extraction; multiplex-PCR was done with primer sequences intended to plasmid-mediated quinolone-resistance genes which is qnrA, qnrB, and qnrS. In this study; it was 21 qur genes amongst 15 isolates. The qnrS gene was the commonest (10/21, 47.6%) followed by qnrA (6/21, 28.5%), whereas only 4 isolates were positive for qnrB (5/21, 23.8%). Some isolates had more than one qnr genes. So, Ciprofloxacin-resistant Salmonella typhi can have more than one gene at the same time; and the most occurrence rate in regards to qnr gene in this study was qnrS compared to qnrA and qnrB

Abstract The present investigation aimed to formulate a liquid self-microemulsifying drug delivery system (SMEDDS) of tacrolimus to enhance its oral bioavailability by improving its dispersibility and dissolution rate. Four liquid SMEDDS were prepared using maisine CC as oil phase, labrasol ALF as surfactant and transcutol HP as co-surfactant based on the solubility studies of tacrolimus in these components. The phase behavior of the components and the area of microemulsion were evaluated using pseudoternary phase diagrams. The formulations were also assessed for thermodynamic stability, robustness to dilution, self-emulsification time, drug content, globule size and polydispersity index. The prepared SMEDDS formulations exhibited improved drug release compared to the pure drug powder. From this study, it was concluded that using a composition of 10% maisine CC, 67.5% labrasol ALF and 22.5% transcutol produced a liquid SMEDDS with good thermodynamic stability and enhanced in-vitro drug release profiles compared with pure tacrolimus powder. All which supports the use of self-micro emulsifying drug delivery systems as a promising approach to improve solubility, dissolution and stability of poorly soluble drugs like tacrolimus.

Abstract Background The thyroid gland contributes immensely to the basal metabolic rate, and hence, thermogenesis in mammals. Its response to the thermal environment is, however, slow and may require several days to adjust. A rapid thyrosuppressive mechanism (“Wolff–Chaikoff” phenomenon; WC) is inducible by high dietary iodine ingestion. The current study aimed to examine the WC on thermophysiology of rats exposed to acute heat stress (HS). Biotelemetry was used to assess real-time core body temperature (T core), locomotive activity (LA) and heart rate (HR) in rats (N = 12). Animals were randomly assigned to two treatment groups: a control (CN) group had ad libitum access to tap water throughout the trial; a second group (KI) received potassium iodide (0.5%) in drinking water, 3 h before HS. Climatic conditions during the 10-day experimental period were set to 4 days at thermoneutrality (TN; T a = 23.60 ± 0.05 °C), then HS (T a = 33.22 ± 0.25 °C, for 4 h) and finally back to TN until the end of trial. Serum samples were collected right after the HS, to measure free thyroxine (FT4), triiodothyronine (FT3) and total antioxidant capacity (TAO), from 12 other equivalent rats. Results The KI induced the WC, as evidenced with lower FT3 (1.66 and 1.91 ± 0.08 pg/mL) than the CN treatment, respectively. This momentary goitrogenic response by KI mitigated hyperthermia, compared to CN (T core maxima of 38.90 and 39.54 ± 0.09 °C). Furthermore, KI resulted in higher TAO than KI-free rats (238.30 and 198.80 ± 9.10 µM copper reducing equivalents). While instigating an instant suppression in LA, KI caused a delayed 25% elevation in HR along with a rebound in T core, likely due to the “escape phenomenon.” Conclusions The employed WC protocol alleviated HS impact on rats. Research on other mammals awaits further investigation.

Cyclosporine is a potent immunosuppressive drug. It has a narrow therapeutic index, and therefore the measurement of cyclosporine’s blood concentration is essential to obtain optimal therapy. Measurement of the area under the blood concentration-time curve (AUC) is reflective of total drug exposure. However, for organ transplant patients, the measurement of AUC involves many problems and difficulties. Thus, it is more clinically acceptable to use a single blood sample as a surrogate index of total drug exposure. Fifty-four adults bone marrow transplant Iraqi patients were given cyclosporine every 12 h as prophylaxis using Neoral® oral solution. Steady-state blood concentrations were monitored for each patient at zero time and then at 1, 2, 3, 4, 6, 8, 10, and at 12 h post-dosing. Cyclosporine blood levels were determined by using AXSYM automated immuno-analyzer which is a fluorescence polarization immunoassay (FPIA). The present investigation demonstrated the best correlation between C2 and the corresponding AUC0−4h and AUC0−12h compared to other concentrations. After two months of cyclosporine therapy, no unexpected biochemical changes and adverse effects were registered. It is concluded from this study that a single blood sample obtained at 2 h post-dosing (C2) and possibly at 3 h post dosing (C3) are ideal surrogate indexes for reflecting total drug exposure, and therefore may be used in clinical practice for predicting therapeutic and toxic effects of cyclosporine.

Betahistine dihydrochloride is widely used to reduce the severity and frequency of vertigo attacks associated with Ménière’s disease. Betahistine is an analogue of histamine, and is a weak histamine H1 receptor agonist and potent histamine H3 receptor antagonist. The recommended therapeutic dose for adults ranges from 24 to 48 mg given in doses divided throughout the day. Betahistine undergoes extensive first-pass metabolism to the major inactive metabolite 2-pyridyl acetic acid (2PAA), which can be considered a surrogate index for quantitation of the parent drug due to extremely low plasma levels of betahistine. The aim of the present investigation was to assess the pharmacokinetics and dose proportionality of betahistine in Arabic healthy adult male subjects under fasting conditions. A single dose of betahistine in the form of a 8, 16, or 24 mg tablet was administered to 36 subjects in randomized, cross-over, three-period, three-sequence design separated by a one week washout period between dosing. The pharmacokinetic parameters Cmax, AUC0−t, AUC0−∞, Tmax, and Thalf were calculated for each subject from concentrations of 2-PAA in plasma, applying non-compartmental analysis. The current study demonstrated that betahistine showed linear pharmacokinetics (dose proportionality) in an Arabic population over the investigated therapeutic dose range of 8−24 mg.

The present study aimed to environmentally friendly synthesis of ZnO NPs using Fioria vitifolia leaf extracts which provides a sustainable and green approach for production of NPs. The produced ZnO NPs were evaluated using various spectrum approaches (UV-vis, FTIR XRD, TEM and EDAX). The synthesized ZnO NPs was confirmed by UV-Visible spectroscopy exhibited a peak at 370 nm. SEM imaging revealed a flash-like and needle-like bottom morphology. Fourier-transform infrared spectroscopy (FTIR) analysis detected vibrations corresponding to alcohols, halides, and aromatics functional groups. TEM showed spherical-shaped NPs with an average diameter of 11 nm. XRD analysis exhibited distinct peaks at 2θ values of 31.7°, 34.3°, 36.2°, 47.4°, 56.6°, 62.8°, 66.4°, 67.9°, 69.1°, and 76.8°, corresponding to the crystallographic planes (100), (002), (101), (102), (110), (103), (200), (112), (201), (004), and (202) planes respectively. The antibacterial activity demonstrated significant zones of inhibition against E. coli (17±0.6 mm) and S. aureus (23.7±0.5 mm), and inhibition of biofilm formation in S. aureus and C. albicans. Additionally, S. mutans exhibited the highest sensitivity to the minimum inhibitory concentration (MIC) of ZnO NPs, with complete inhibition occurring at 7.5 μg/mL. Furthermore, antioxidant DPPH assays exhibited IC 50 values of 42 μg/mL. Additionally, the anti-inflammatory properties of ZnO NPs of F. vitifolia were evaluated in-vitro using models utilizing the human red blood cells (HRBC) membrane stabilization method (MSM), and it was shown to have an MSM of 83.87% at 250 μg/mL. Furthermore, ZnO NPs exhibited anticancer activity against the MDA-MB-231 breast cancer cell line with an IC 50 value of 35.50 μg/mL. Toxicological evaluation of FV-ZnO nanoparticles in zebrafish (Danio rerio) embryos indicated low toxicity at maximum concentration. These is first findings suggest that ZnO NPs synthesized from F. vitifolia leaf extracts possess significant antibacterial, antioxidant, anti-inflammatory, and anticancer properties. Additionally, their low toxicity in zebrafish embryos makes them suitable for further development in antimicrobial therapies with minimal side effects, offering a sustainable, biocompatible solution to tackle multidrug-resistant microbial infections., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Breast cancer is a serious concern for many women worldwide. Drug-loaded implants have shown several benefits over systemic administrations. To provide anti-cancer drugs with controlled release and reduced systemic toxicity, biodegradable in situ implants have attracted a lot of attention. In the present study, we aimed to design and optimize a doxorubicin-loaded chitosan-poloxamer in situ implant for breast cancer treatment. Utilizing Box-Behnken Design and a Quality-by-Design (QbD) methodology, the in situ implant was prepared with chitosan (X1), poloxamer 407 concentration (X2), and stirring time (X3) as the independent variables. It was characterized for its in vitro gelation time, pH, rheology, and morphology, and evaluated based on drug release profile, in vitro cytotoxicity activities, in vitro anti-inflammatory potential, in vitro cellular uptake, and in vivo anti-inflammatory and pharmacokinetics to ensure their therapeutic outcomes. The results revealed that the prepared formulation showed a gelation time of 26 ± 0.2 s with a viscosity of 8312.6 ± 114.2 cPs at 37 °C. The developed formulation showed better cytotoxic activity in MCF-7 cell lines compared to the free drug solution. It demonstrated reduced levels of pro-inflammatory cytokines in RAW 264.7 macrophages. Further, the prepared in situ implant increases the intracellular accumulation of DOX in the MCF-7 cells. The in vivo pharmacokinetic investigations depicted an increase in t 1/2 and a decrease in AUC of the developed formulation resulting in prolonged drug release and there could be a lower drug concentration in the bloodstream than for the free drug. Therefore, the developed in situ implant may offer a viable option for breast cancer treatment., Competing Interests: The authors declare no conflict of interest, (This journal is © The Royal Society of Chemistry.)

The study aimed to verify the pathogenic malarial kidney infections and histopathological pictures in mice infected with Plasmodium chabaudi using Indigofera oblongifolia leaf extract silver nanoparticles (IOLEAgNPs). Fifty healthy adult female mice C57BL/6 were used. Animals were divided into five groups, with each group of ten mice. The first control non-infected group was given distilled water for 7 days. The second group was orally given 50 mg/kg of IOLEAgNPs. The third, fourth, and fifth groups were injected intraperitoneally with 10 5 parasitized erythrocytes of P. chabaudi . After 1 h, the fourth group received 50 mg/kg of IOLEAgNPs, while the fifth group orally received 10 mg/kg chloroquine phosphate. The histopathology of the kidney was studied by routine histology method with hematoxylin-eosin staining. The kidney revealed cerebral microvessel congestion, hemorrhages, and necrosis. Cast formation, glomerulonephritis, tubular necrosis, and congestion were observed in the kidney cortex. Consequently, the targeted medical IOLEAgNPs reduced this degeneration impact on renal tissue. Proven that plant-source synthesized IOLEAgNPs play a preventive role as antimalarial agents in female mice infected with P. chabaudi., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter.)

l-cysteine is a versatile amino acid that plays a pivotal role in synthesizing critical molecules, enzymatic catalysis, regulation, and electron transport. It also has tremendous potential to act as an adjuvant for enhancing the biological efficacy of various nanoparticles in vivo. The current study is aimed to evaluate the protective efficacy of silver nanoparticles (AgNPs) decorated with l-cysteine in carbon tetrachloride (CCl 4 )-induced hepatotoxicity in the Swiss albino rats as an animal model. The rats were divided into four treatment groups: Group 1 (control without any treatments), Group 2 treated with AgNPs and l-cysteine composite (5 mg/kg body weight on every third day), Group 3 (single dose of 1 mL/kg CCl 4 ), and Group 4 treated with AgNPs-l-cysteine composite in the rats pre-administered with CCl 4 . After treatment for a month, the rats were killed, and their liver and blood samples were subjected to biochemical analysis and histological examination.: Group 2 showed all the parameters comparable to control Group 1. On the contrary, CCl 4 -treated, Group 3 rats showed abnormally raised liver function markers (AST and ALT) and liver toxicity markers (GGT, LDH, and total bilirubin) concomitant with disturbed oxidative stress parameters (GSH and MDA) compared to the control. However, Group 4 rats demonstrated a significant recovery from CCl 4 -induced biochemical alteration in the animals as compared to Group 3. In addition, the biochemical measurements were harmonious with the histological analysis of the liver sections of the treated rats. Hence, the proposed AgNPs-l-cysteine composite is a potent hepato-protecting agent in vivo that can be employed in regulating CCl 4 -induced hepatotoxicity or any drug or potential pharmaceutical compound exerting similar toxicity., (© 2024 John Wiley & Sons Ltd.)

Background: Immune checkpoints are receptors on the surface of T cells that function crucially in suppressing the immune response, and they are implicated in autoimmunity and cancer diseases., Aim: The present study aimed to investigate the relationship between functional single nucleotide polymorphisms (SNPs) of two immune checkpoint molecules, CTLA-4 and TIM-3, and acute myeloid leukemia (AML) in a Saudi population., Methods: Two SNPs in CTLA-4 (rs231775, A > G) and TIM-3 (rs10515746, A > C) were genotyped in 229 subjects, including 98 patients and 131 healthy controls, from the Saudi population using TaqMan assay methods. Differential expression of these two genes was performed using in silico analysis., Results: An association was found between polymorphisms in TIM-3 (OR: 6.01; 95% CI: 3.99-9.05, P  < 0.0001) and the risk of AML. Inversely, the rs231775 SNP in the CTLA-4 gene was found to protect against AML in allelic, dominant, and additive models ( P  < 0.05). A significantly higher expression of TIM-3 in the blood of individuals with AML was observed., Conclusion: This is the first study focusing on single nucleotide polymorphisms (SNPs) for CTLA-4 and TIM-3 in acute myeloid leukemia patients in a Saudi community and could be a potential new prognostic factor for this disease.

The intricate process of protein binding orchestrates crucial drug interactions within the bloodstream, facilitating the formation of soluble complexes. This research endeavours to improve the dissolution and oral bioavailability of Rifampicin (RMP) by strategically manipulating drug-protein binding dynamics and the hydrophobic characteristics of human serum albumin (HSA). Various precipitation techniques leveraging methanol, ammonium sulfate, and heat treatment were meticulously employed to tailor the properties of colloidal albumin (HSA NPs). The resultant complexes underwent comprehensive characterization encompassing evaluations of hydrophobicity, size distribution, surface charge, and structural analyses through FTIR, TG-DSC, XRD, and morphological examinations. The findings revealed a significant binding affinity of 78.07 ± 6.6% with native albumin, aligning with prior research. Notably, the complex RMP-HSA NPs-M13, synthesized via the methanolic precipitation method, exhibited the most substantial complexation, achieving a remarkable 3.5-fold increase, followed by the ammonium sulfate (twofold) and heat treatment (1.07-fold) methods in comparison to native albumin binding. The gastric simulated media exhibited accelerated drug release kinetics, with maximal dissolution achieved within two hours, contrasting with the prolonged release observed under intestinal pH conditions. These findings translated into significant improvements in drug permeation, as evidenced by pharmacokinetic profiles demonstrating elevated Cmax, AUC, t1/2, and MRT values for RMP-HSA NPs-M13 compared to free RMP. In summary, this innovative approach underscores the potential of precipitation methods in engineering stable colloidal carrier systems tailored to enhance the oral bioavailability of poorly soluble drugs, offering a pragmatic and scalable alternative to conventional surfactants, polymers, or high-energy methods for complex formation and production., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Abnormal deposition of Aβ amyloid is an early neuropathological marker of Alzheimer's disease (AD), arising long ahead of clinical symptoms. Non-invasive measures of associated early neurofunctional changes, together with easily accessible behavioral readouts of these changes, could be of great clinical benefit. We pursued this aim by investigating large-scale cortical gradients of functional connectivity with functional MRI, which capture the hierarchical integration of cortical functions, together with acoustic-prosodic features from spontaneous speech, in cognitively unimpaired older adults with and without Aβ positivity (total N = 188). We predicted distortions of the cortical hierarchy associated with prosodic changes in the Aβ + group. Results confirmed substantially altered cortical hierarchies and less variability in these in the Aβ + group, together with an increase in quantitative prosodic measures, which correlated with gradient variability as well as digit span test scores. Overall, these findings confirm that long before the clinical stage and objective cognitive impairment, increased risk of cognitive decline as indexed by Aβ accumulation is marked by neurofunctional changes in the cortical hierarchy, which are related to automatically extractable speech patterns and alterations in working memory functions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and objectives: Acute myeloid leukemia (AML) is a hematological malignancy characterized by uncontrolled proliferation of immature myeloid cells. Immune checkpoint molecules such as programmed cell death protein 1 (PD-1) and lymphocyte activation gene-3 (LAG-3) are essential for controlling anti-tumor immune responses. This study aims to explore the correlation between specific genetic variations (SNPs) in the PDCD1 (rs2227981) and LAG3 (rs12313899) genes and the likelihood of developing AML in the Saudi population. Material and methods : total of 98 Saudi AML patients and 131 healthy controls were genotyped for the PDCD1 rs2227981 and LAG3 rs12313899 polymorphisms using TaqMan genotyping assays. A logistic regression analysis was conducted to evaluate the relationship between the SNPs and AML risk using several genetic models. Results : The results revealed a significant association between the PDCD1 rs2227981 polymorphism and increased AML risk. In AML patients, the frequency of the G allele was considerably greater than in healthy controls (OR = 1.93, 95% CI: 1.31-2.81, p = 0.00080). The GG and AG genotypes were associated with a very high risk of developing AML ( p < 0.0001). In contrast, no significant association was observed between the LAG3 rs12313899 polymorphism and AML risk in the studied population. In silico analysis of gene expression profiles from public databases suggested the potential impact of PDCD1 expression levels on the overall survival of AML patients. Conclusions : This study provides evidence for the association of the PDCD1 rs2227981 polymorphism with an increased risk for AML in the Saudi population.

Research on various languages shows that dynamic approaches to vowel acoustics - in particular Vowel-Inherent Spectral Change (VISC) - can play a vital role in characterising and classifying monophthongal vowels compared with a static model. This study's aim was to investigate whether dynamic cues also allow for better description and classification of the Hijazi Arabic (HA) vowel system, a phonological system based on both temporal and spectral distinctions. Along with static and dynamic F1 and F2 patterns, we evaluated the extent to which vowel duration, F0, and F3 contribute to increased/decreased discriminability among vowels. Data were collected from 20 native HA speakers (10 females and 10 males) producing eight HA monophthongal vowels in a word list with varied consonantal contexts. Results showed that dynamic cues provide further insights regarding HA vowels that are not normally gleaned from static measures alone. Using discriminant analysis, the dynamic cues (particularly the seven-point model) had relatively higher classification rates, and vowel duration was found to play a significant role as an additional cue. Our results are in line with dynamic approaches and highlight the importance of looking beyond static cues and beyond the first two formants for further insights into the description and classification of vowel systems., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Hepatotoxicity is one of the significant side effects of chronic diabetes mellitus (DM) besides nephrotoxicity and pancreatitis. The management of this disease is much dependent on the restoration of the liver to its maximum functionality, as it is the central metabolic organ that gets severely affected during chronic diabetes. The present study investigates if the silver nanoparticles decorated with curcumin (AgNP-Cur) can enhance the efficacy of metformin (a conventional antidiabetic drug) by countering the drug-induced hepatoxicity. Swiss albino rats were categorized into six treatment groups ( n = 6): control (group I without any treatment), the remaining five groups (group II, IV, V, VI) were DM-induced by streptozocin. Group II was untreated diabetic positive control, whereas groups III was administered with AgNP-cur (5 mg/kg). Diabetic group IV treated with metformin while V and VI were treated with metformin in a combination of the two doses of NPs (5 and 10 mg/kg) according to the treatment schedule. Biochemical and histological analysis of blood and liver samples were conducted after the treatment. The groups V and VI treated with the combination exhibited remarkable improvement in fasting glucose, lipid profile (HDL and cholesterol), liver function tests (AST, ALT), toxicity markers (GGT, GST and LDH), and redox markers (GSH, MDA and CAT) in comparison to group II in most of the parameters. Histological evaluation and comet assay further consolidate these biochemical results, pleading the restoration of the cellular structure of the target tissues and their nuclear DNA. Therefore, the present study shows that the NPs can enhance the anti-diabetic action by suppression of the drug-mediated hepatoxicity via relieving from oxidative stress, toxic burden and inflammation.

Background: Decline in language has emerged as a new potential biomarker for the early detection of Alzheimer's disease (AD). It remains unclear how sensitive language measures are across different tasks, language domains, and languages, and to what extent changes can be reliably detected in early stages such as subjective cognitive decline (SCD) and mild cognitive impairment (MCI)., Method: Using a scene construction task for speech elicitation in a new Spanish/Catalan speaking cohort ( N = 119), we automatically extracted features across seven domains, three acoustic (spectral, cepstral, and voice quality), one prosodic, and three from text (morpholexical, semantic, and syntactic). They were forwarded to a random forest classifier to evaluate the discriminability of participants with probable AD dementia, amnestic and nonamnestic MCI, SCD, and cognitively healthy controls. Repeated-measures analyses of variance and paired-samples Wilcoxon signed-ranks test were used to assess whether and how performance differs significantly across groups and linguistic domains., Results: The performance scores of the machine learning classifier were generally satisfactorily high, with the highest scores over .9. Model performance was significantly different for linguistic domains ( p < .001), and speech versus text ( p = .043), with speech features outperforming textual features, and voice quality performing best. High diagnostic classification accuracies were seen even within both cognitively healthy (controls vs. SCD) and MCI (amnestic and nonamnestic) groups., Conclusion: Speech-based machine learning is powerful in detecting cognitive decline and probable AD dementia across a range of different feature domains, though important differences exist between these domains as well., Supplemental Material: https://doi.org/10.23641/asha.23699733.

Hepatocellular carcinoma (HCC) is the second-largest cause of death among all cancer types. Many drugs have been used to treat the disease for a long time but have been mostly discontinued because of their side effects or the development of resistance in the patients with HCC. The administration of DZ orally is a great focus to address the clinical crisis. Daidzein (DZ) is a prominent isoflavone polyphenolic chemical found in soybeans and other leguminous plants. It has various pharmacological effects, including anti-inflammatory, antihemolytic, and antioxidant. This present study investigates the protective effect of DZ on chemically induced HCC in rat models. The DZ was administered orally four weeks before HCC induction and continued during treatment. Our study included four treatment groups: control (group 1, without any treatment), HCC-induced rats (group II), an HCC group treated with DZ at 20 mg/kg (group III), and an HCC group treated with DZ at 40 mg/kg (group IV). HCC rats showed elevation in all the HCC markers (AFP, GPC3, and VEGF), liver function markers (ALP, ALT, and AST), inflammatory markers (IL-6, TNF-α, and CRP), and lipid markers concomitant with a decrease in antioxidant enzymes and protein. However, groups III and IV demonstrated dose-dependent alleviation in the previous parameters resulting from HCC. In addition, the high dose of DZ reduces many hepatological changes in HCC rats. All study parameters improved with DZ administration. Due to its antioxidant and anti-inflammatory characteristics, DZ is a promising HCC treatment option for clinical use.

Potassium bromate (PB) is a general food additive, a significant by-product during water disinfection, and a carcinogen (Class II B). The compound emits toxicity depending on the extent of its exposure and dose through consumable items. The current study targeted disclosing the ameliorative efficacy of zinc oxide nanoparticles (ZnO NPs) prepared by green technology in PB-exposed Swiss albino rats. The rats were separated into six treatment groups: control without any treatment (Group I), PB alone (Group II), ZnO alone (Group III), ZnO NP alone (Group IV), PB + ZnO (Group V), and PB + ZnO NPs (Group VI). The blood and kidney samples were retrieved from the animals after following the treatment plan and kept at -20 °C until further analysis. Contrary to the control (Group I), PB-treated rats (Group II) exhibited a prominent trend in alteration in the established kidney function markers and disturbed redox status. Further, the analysis of the tissue and nuclear DNA also reinforced the biochemical results of the same treatment group. Hitherto, Groups III and IV also showed moderate toxic insults. However, Group VI showed a significant improvement from the PB-induced toxic insults compared to Group II. Hence, the present study revealed the significant therapeutic potential of the NPs against PB-induced nephrotoxicity in vivo, pleading for their usage in medicines having nephrotoxicity as a side effect or in enhancing the safety of the industrial use of PB.

Coccidiosis is a parasitic infection threatening poultry products globally. Parasite resistance to drugs is one of the barriers to Eimeria control. Natural products are one of the sources of compounds that prevent parasite infections. The current study was, therefore, conducted to evaluate the effect of Vitis vinifera leaf extract on anti-inflammatory response, oxidative status, and goblet cell response against Eimeria papillate infection in mice. Methanol was used as a solvent for phytochemicals. The mice were divided into six groups: The first group was the control. The second group was uninfected and treated with 200 mg/kg of extract to test toxicity, and the third, fourth, fifth, and sixth groups of mice received 1 × 10 3 sporulated E. papillate oocysts. The third group received no treatment. The fourth and fifth groups were treated daily with 100 and 200 mg/kg of V. vinifera leaf extract, respectively, while the sixth group received 25 mg/kg of toltrazuril daily via gavage. On day 5 p.i., the animals were sacrificed, and jejunum samples were prepared for analyses of histological sections and oxidative stress. The phytochemical analysis using GC-MS of the extract showed the presence of 12 biologically active compounds. The most effective dose was 200 mg/kg, which significantly decreased the number of parasitic stages in the jejunal sections of the mice. The findings demonstrate that E. papillate infection in mice results in significant histopathological changes in the jejunum, including inflammation, epithelial vacuolation, villi loss, and a decrease in goblet cell density. When infected mice received treatment, the histological injury score within the infected jejunum tissue decreased by 63%, and the goblet cell quantity dramatically increased, approaching the control values. Finally, the extract ameliorated the changes in glutathione and malondialdehyde due to E. papillate infection. The extract was proven to have anti-inflammatory properties and reduce the number of oocysts. Overall, the findings show that V. vinifera leaf extract has significant anticoccidial effects in vivo.

The efficacy of anticancer drug 5-FU is suppressed due to various factors, including severe side effects and decreased insensitivity during prolonged chemotherapy. Elevated endogenous copper (Cu) levels are one of the prominent hallmark features of cancer cells. In the present investigation, this feature was targeted in diethyl nitrosamine-phenobarbital-induced hepatocellular carcinoma (HCC) in a rat model system by an established anticancer drug, 5-FU, co-administered with copper and its chelating agent, disulfiram. After treatment with the test chemicals in HCC-induced rats, blood and liver samples were subjected to biochemical, molecular, and histopathological analyses. The analysis revealed that reactive oxygen species-mediated oxidative stress is the crucial etiological reason for the pathogenesis of HCC in rats, as evidenced by the significantly compromised activity of major antioxidant enzymes and elevated levels of oxidative damaged products with major histological alterations compared to the control. However, the combination of 5-FU with DSF demonstrated a significant improvement in most of the parameters, followed by 5-FU-Cu in the combination-treated groups. The combination treatment improved the histological details and triggered apoptosis in the cancer cells to a remarkable extent, as the levels of cleaved PARP and caspase-3 were significantly higher than those in the HCC rats treated with the drug alone. The present study envisages that manipulating the Cu-level greatly enhances the antineoplastic activity of 5-FU and sensitizes cancer cells to the increased efficacy of the drug.

Purpose: Myxozoans are economically important group of metazoan parasites, which can cause diseases in a large variety of commercially important fishes. Increased knowledge on molecular features has shown that traditional descriptive characters may be misleading. Combination of both descriptive and molecular features is therefore necessary for an integrated taxonomic assessment., Methods: Cyprinid Labeo batesii, sampled in the Makombè River at Nkondjock in Cameroon were examined for myxosporeans. Identification of parasite species was based on morphological and molecular sequence analyses of myxospores. Phylogenetic analysis was performed using maximum likelihood (ML) and Bayesian inference (BI) methods., Results: The scales of L. batesii were infected by Myxobolus nkondjockei sp. nov Their mature myxospores are ovoid in frontal view and lenticular in lateral view, with two rounded ends. These myxospores measured 10.3 (10-10.9) μm length and 8.0 (7.3-8.5) μm width. Myxospores have two ovoid and equal sizes polar capsules. They measured 4.5 (4.0-5.0) µm in length and 2.4 (2-2.9) µm in width. Polar tubules were coiled in 4-5 turns perpendicular to the longitudinal axis of the polar capsules. Phylogenetic analysis of the 18S rDNA sequence show clustering of M. nkondjockei sp. n. close to an undetermined species Myxobolus sp. reported infecting gill lamellas of Labeo rohita from India., Conclusion: The morphological, molecular and phylogenetic data provided for M. nkondjockei sp. n. are solid basis for further identification of this myxozoan of which pathogenicity probably plays an economic role at culturing the hosts., (© 2022. The Author(s) under exclusive licence to Witold Stefański Institute of Parasitology, Polish Academy of Sciences.)

A series of novel 3-phenyl-1-(alkylphenyl)-9-oxa-4-azaphenanthren-10-ones and (E)-1-phenyl-3-(aryl)prop-2-en-1-ones were synthesized and characterized by IR, 1 H NMR, 13 C spectroscopy and elemental analysis. The synthesized Compounds 5a-f were subjected to molecular docking simulation with three proteins, namely, tyrosyl-tRNA synthetase, heme oxygenase 1 and acetylcholinesterase to evaluate the antibacterial, antioxidant and acetylcholinesterase inhibition, respectively. Moreover, the docked poses of all compounds inside the proteins were subjected to further dynamic simulation through the calculation of the binding free energy using MM-GBSA analysis. Compound 5d exhibits high potential inhibition against antibacterial, antioxidant and acetylcholinesterase activities. Compounds 3d , 3f , 5a and 5d recorded an important scavenging activity in DPPH and ABTS assays. Investigation of the anti-acetylcholinesterase activity of the synthesized compounds showed that Compounds 5a and 3d are the most potent inhibitors against AchE, with percent inhibition values of 38 and 30%, respectively.Communicated by Ramaswamy H. Sarma.