Divalent metal ion in the active site of purple acid phosphatase modulates substrate binding: Kinetic and thermodynamic properties.

The purple acid phosphatase was purified from 5.9-fold to apparent homogeneity from Anagelis arvensis seeds using SP-Sephadex C-50 and Sephadex G-100 chromatography. The results of residual activity tests conducted using different temperature ranges (50-70 °C) were calculated as the activation energy (Ed = 72 kJ/mol), enthalpy (69.31 ≤ (ΔH° ≤ 69.10 kJ/mol), entropy (-122.48 ≤ ΔS° ≤ -121.13 J/mol·K), and Gibbs free energy (108.87 ≤ ΔG° ≤ 111.25 kJ/mol) of the enzyme irreversible denaturation. These thermodynamic parameters indicate that this novel PAP is highly thermostable and may be significant for use in industrial applications. However, it may be confirmed by stopped-flow measurements that this substitution produces a chromophoric Fe3+ site and a Pi-substrate interaction that is about ten times faster. Additionally, these data show that phenyl phosphate hydrolysis proceeds more rapidly in metal form of A. arvensis PAP than the creation of a µ-1,3 phosphate complex. The Fe3+ site in the native Fe3+-Mn2+ derivative interacts with it at a faster rate than in the Fe3+-Fe2+ form. This is most likely caused by a network of hydrogen bonds between the first and second coordination spheres. This suggests that the choice of metal ions plays a significant role in regulating the activity of this enzyme.

Tracking the epidemiological trends of female breast cancer in Saudi Arabia since 1990 and forecasting future statistics using global burden of disease data, time-series analysis.

BACKGROUND: Female breast cancer stands as the prime type of cancer in the Kingdom of Saudi Arabia (KSA), with a high incidence and mortality rates. This study assessed the burden of female breast cancer in KSA by analyzing and forecasting its incidence, mortality, and disability-adjusted life years (DALYs). METHODS: We retrieved data from the Global Burden of Disease (GBD) about female breast cancer from 1990 to 2021. Time-series analysis used the autoregressive integrated moving average (ARIMA) model to forecast female breast cancer statistics from 2022 to 2026. RESULTS: From 1990 to 2021, KSA reported 77,513 cases of female breast cancer. The age groups with the highest number of cases are 45-49 years, followed by 40-44 years, 50-54 years, and 35-39 years. The analysis also showed fewer cases in the younger age groups, with the lowest number in the less than 20-year-old age group. From 1990 to 2021, KSA reported 19,440 deaths due to breast cancer, increasing from 201 cases in 1990 to 1,190 cases in 2021. The age-standardized incidence rate/100,000 of breast cancer increased from 15.4 (95% confidence interval (CI) 11.2-21.0) in 1990 to 46.0 (95%CI 34.5-61.5) in 2021. The forecasted incidence rate of female breast cancer will be 46.5 (95%CI 45.8-46.5) in 2022 and 49.6 (95%CI 46.8-52.3) in 2026. The age-standardized death rate per 100,000 Saudi women with breast cancer increased from 6.73 (95%CI 6.73-9.03) in 1990 to 9.77 (95%CI 7.63-13.00) in 2021. The forecasted female breast cancer death rate will slightly decrease to 9.67 (95%CI 9.49-9.84) in 2022 and to 9.26 (95%CI 8.37-10.15) in 2026. DALYs increased from 229.2 (95%CI 165.7-313.6) in 1990 to 346.1 (95%CI 253.9-467.2) in 2021. The forecasted DALYs of female breast cancer will slightly decrease to 343.3 (95%CI 337.2-349.5) in 2022 reaching 332.1 (95%CI 301.2-363.1) in 2026. CONCLUSIONS: Female breast cancer is still a significant public health burden that challenges the health system in KSA, current policies and interventions should be fashioned to alleviate the disease morbidity and mortality and mitigate its future burden.

Revitalizing oral cancer research: Crispr-Cas9 technology the promise of genetic editing.

This review presents an in-depth analysis of the immense potential of CRISPR-Cas9 technology in revolutionizing oral cancer research. It underscores the inherent limitations of conventional treatments while emphasizing the pressing need for groundbreaking approaches. The unparalleled capability of CRISPR-Cas9 to precisely target and modify specific genes involved in cancer progression heralds a new era in therapeutic intervention. Employing genome-wide CRISPR screens, vulnerabilities in oral cancer cells can be identified, thereby unravelling promising targets for therapeutic interventions. In the realm of oral cancer, the disruptive power of CRISPR-Cas9 manifests through its capacity to perturb genes that are intricately associated with drug resistance, consequently augmenting the efficacy of chemotherapy. To address the challenges that arise, this review diligently examines pertinent issues such as off-target effects, efficient delivery mechanisms, and the ethical considerations surrounding germline editing. Through precise gene editing, facilitated by CRISPR/Cas9, it becomes possible to overcome drug resistance by rectifying mutations, thereby enhancing the efficacy of personalized treatment strategies. This review delves into the prospects of CRISPR-Cas9, illuminating its potential applications in the domains of medicine, agriculture, and biotechnology. It is paramount to emphasize the necessity of ongoing research endeavors and the imperative to develop targeted therapies tailored specifically for oral cancer. By embracing this comprehensive overview, we can pave the way for ground-breaking treatments that instill renewed hope for enhanced outcomes in individuals afflicted by oral cancer.

Integration of a Randomized Sequence Scanning Approach in AlphaFold2 and Local Frustration Profiling of Conformational States Enable Interpretable Atomistic Characterization of Conformational Ensembles and Detection of Hidden Allosteric States in the ABL1 Protein Kinase.

Despite the success of AlphaFold methods in predicting single protein structures, these methods showed intrinsic limitations in the characterization of multiple functional conformations of allosteric proteins. The recent NMR-based structural determination of the unbound ABL kinase in the active state and discovery of the inactive low-populated functional conformations that are unique for ABL kinase present an ideal challenge for the AlphaFold2 approaches. In the current study, we employ several adaptations of the AlphaFold2 methodology to predict protein conformational ensembles and allosteric states of the ABL kinase including randomized alanine sequence scanning combined with the multiple sequence alignment subsampling proposed in this study. We show that the proposed new AlphaFold2 adaptation combined with local frustration profiling of conformational states enables accurate prediction of the protein kinase structures and conformational ensembles, also offering a robust approach for interpretable characterization of the AlphaFold2 predictions and detection of hidden allosteric states. We found that the large high frustration residue clusters are uniquely characteristic of the low-populated, fully inactive ABL form and can define energetically frustrated cracking sites of conformational transitions, presenting difficult targets for AlphaFold2. The results of this study uncovered previously unappreciated fundamental connections between local frustration profiles of the functional allosteric states and the ability of AlphaFold2 methods to predict protein structural ensembles of the active and inactive states. This study showed that integration of the randomized sequence scanning adaptation of AlphaFold2 with a robust landscape-based analysis allows for interpretable atomistic predictions and characterization of protein conformational ensembles, providing a physical basis for the successes and limitations of current AlphaFold2 methods in detecting functional allosteric states that play a significant role in protein kinase regulation.

Cardiotoxicity in Cancer Patients: The Prevalence, Risk Factors, and Cardioprotective Measures in a Cancer Centre in Saudi Arabia.

BACKGROUND: Chemotherapy-related cardiotoxicity can exhibit several patterns of functional, structural, and vascular complications. This study aims to identify the patterns and the factors associated with cardiotoxicity in cancer patients. METHOD: A retrospective cross-sectional analysis of 96 adult cancer patients undergoing anticancer therapy was investigated at King Khalid Hospital in Najran, Saudi Arabia, from May 2022 to April 2023. The data on patient and cancer characteristics, treatment, and outcomes were collected and analyzed. Factors associated with cardiotoxicity were investigated through univariate analyses using odds ratio (OR) and 95% confidence interval (CI). RESULTS:  Among the 96 cancer patients in the study, cardiotoxicity occurred in 12 individuals (12.5%). The mean age was 57.0 ± 13.3 years (range: 32-81 years), with 32 (33.3%) being above 65 years. The most common comorbidities were diabetes (n=48; 50%), followed by hypertension (n=32; 33.3%), and dyslipidemia (n=20; 20.8%). The most common cancers were gastrointestinal cancer (n=32; 33.3%), followed by breast cancer (n=22; 22.9%) and lymphoma (n=14; 14.6%). Females were disproportionately affected (64.6%), with 57.3% of them in the metastatic stage. The majority of patients (90.6%) had normal ejection fraction before chemotherapy initiation. In univariate analysis, current smoking (OR: 7.00; 95%CI: 1.94-25.25, p= 0.003), history of percutaneous cardiac intervention (OR: 40.24; 95%CI: 1.80-896.26, p= 0.019), diabetes (OR: 6.05; 95%CI: 1.24-29.32, p= 0.025), renal failure (OR: 8.20; 95%CI: 0.91-74.88, p= 0.046), dyslipidemia (OR: 5.00; 95 CI: 1.38-18.32, p=0.012), anthracycline use (OR: 18.33; 95%CI: 4.36-126.55, p <0.001), trastuzumab use (OR: 25.00; 95%CI: 6.25-129.86, p < 0.001), and increased chemotherapy cycles number (> 10 cycles) (OR: 73.00; 95%CI: 8.56- 622.36, p < 0.001) were associated with cardiotoxicity. Additionally, beta-blocker use was associated with lower rates of cardiotoxicity (OR: 0.17; 95%CI: 0.036-0.84, p= 0.029). CONCLUSIONS: The incidence of cardiotoxicity among cancer patients treated with chemotherapy is modest, difficult to predict, and independent of baseline cardiac systolic functions. Factors associated with cardiotoxicity include smoking, history of percutaneous cardiac intervention, diabetes, renal failure, dyslipidemia, anthracycline or trastuzumab use, and increased chemotherapy cycle numbers. A combination of various anticancer drugs and chemotherapy may dramatically raise the risk of cardiotoxicity in cancer patients. As a result, patients receiving high-risk cardiotoxic drugs should be monitored with caution to avoid drug-related cardiotoxicity. Furthermore, proactive treatment techniques aiming at reducing the possible cardiotoxic effects of anticancer therapy are critical.

Folliculotropic mycosis fungoides associated with follicular mucinosis: A case report and mini review.

Key Clinical Message: F-MF is a rare non-classic variant of MF. In the case of hair loss, this should be a diagnostic consideration. The essence of the diagnosis of F-MF is a careful medical history, physical examination, and a combination of immunohistological and molecular analyses (Cureus. 2022; 14:e21231, Ann Saudi Med. 2012; 32:283, Oman Med J. 2012; 27:134, Int J Dermatol. 2016; 55:1396, Saudi Med J. 2018; 39:994 and Case Rep Oncol. 2018; 11:436). Abstract: Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma with multiple subtypes. Follicular MF (F-MF) is a non-classic variant of MF. Histological features entail folliculotropism and damage of the epithelium lining of the hair follicles with or without mucin deposition. A 52-year-old male patient complained of recurrent skin lesions on the scalp over 8 months. The lesions appeared suddenly, enlarged over time, and became itchy. A skin punch biopsy was performed. Histological features included mucin deposits in the epithelium of the hair follicles and dense, predominantly perifollicular atypical lymphocytes infiltrating the follicular epithelium. The lymphoid cells were composed of CD3-positive T cells (CD4/CD8-positive T cells) with a shift in favor of the former. The case was diagnosed as F-MF on an immunohistological basis. The diagnosis of F-MF is often difficult for dermatologists and dermatopathologists alike. Not only clinicopathological correlations but also immunohistochemical and molecular analysis are required.

Comparative phenotypic and genotypic analysis of community-acquired and hospital-acquired intra-abdominal infections among liver transplanted patients.

AIM: During liver transplantation, both hospital-acquired (HA) and community-acquired (CA) intra-abdominal infections (IAIs) are involved causing life-threatening diseases. Therefore, comparative studies of aerobic and facultative anaerobic HA-IAIs and CA-IAIs after liver transplantation surgery are necessary. METHODS AND RESULTS: The species of detected isolates (310) from intra-abdominal fluid were identified and classified into hospital-acquired intra-abdominal infections (HA-IAIs) and community-acquired intra-abdominal infections (CA-IAIs). Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii were the most commonly detected species. The resistant phenotypes were commonly detected among the HA-IAIs; however, the virulent phenotypes were the predominant strains of CA-IAIs. Regrettably, the resistance profiles were shocking, indicating the inefficacy of monotherapy in treating these isolates. Therefore, we confirmed the use of empirical combination therapies of amikacin and meropenem for treating all IAIs (FICI ≤ 0.5). Unfortunately, the high diversity and low clonality of all identified HA and CA-IAIs were announced with D-value in the range of 0.992-1. CONCLUSION: This diversity proves that there are infinite numbers of infection sources inside and outside healthcare centers.

Analysis of dermoscopy images of multi-class for early detection of skin lesions by hybrid systems based on integrating features of CNN models.

Skin cancer is one of the most fatal skin lesions, capable of leading to fatality if not detected in its early stages. The characteristics of skin lesions are similar in many of the early stages of skin lesions. The AI in categorizing diverse types of skin lesions significantly contributes to and helps dermatologists to preserve patients' lives. This study introduces a novel approach that capitalizes on the strengths of hybrid systems of Convolutional Neural Network (CNN) models to extract intricate features from dermoscopy images with Random Forest (Rf) and Feed Forward Neural Networks (FFNN) networks, leading to the development of hybrid systems that have superior capabilities early detection of all types of skin lesions. By integrating multiple CNN features, the proposed methods aim to improve the robustness and discriminatory capabilities of the AI system. The dermoscopy images were optimized for the ISIC2019 dataset. Then, the area of the lesions was segmented and isolated from the rest of the image by a Gradient Vector Flow (GVF) algorithm. The first strategy for dermoscopy image analysis for early diagnosis of skin lesions is by the CNN-RF and CNN-FFNN hybrid models. CNN models (DenseNet121, MobileNet, and VGG19) receive a region of interest (skin lesions) and produce highly representative feature maps for each lesion. The second strategy to analyze the area of skin lesions and diagnose their type by means of CNN-RF and CNN-FFNN hybrid models based on the features of the combined CNN models. Hybrid models based on combined CNN features have achieved promising results for diagnosing dermoscopy images of the ISIC 2019 dataset and distinguishing skin cancers from other skin lesions. The Dense-Net121-MobileNet-RF hybrid model achieved an AUC of 95.7%, an accuracy of 97.7%, a precision of 93.65%, a sensitivity of 91.93%, and a specificity of 99.49%.

Dermoscopy aids in lesion selection for microbiological and histopathological assessment of mycetoma.

Mycetoma, a chronic granulomatous infection of the skin and the subcutaneous tissue, is characterized by discharge of exudate containing grains. This report illustrates the importance of dermoscopy in selecting lesions for both microbiological and histopathological assessment, which are considered the gold standard of diagnosis in mycetoma.

Ceiba pentandra ethyl acetate extract improves doxorubicin antitumor outcomes against chemically induced liver cancer in rat model: a study supported by UHPLC-Q-TOF-MS/MS identification of the bioactive phytomolecules.

Hepatocellular carcinoma (HCC) is a prevalent cancer worldwide. Late-stage detection, ineffective treatments, and tumor recurrence contribute to the low survival rate of the HCC. Conventional chemotherapeutic drugs, like doxorubicin (DOX), are associated with severe side effects, limited effectiveness, and tumor resistance. To improve therapeutic outcomes and minimize these drawbacks, combination therapy with natural drugs is being researched. Herein, we assessed the antitumor efficacy of Ceiba pentandra ethyl acetate extract alone and in combination with DOX against diethylnitrosamine (DENA)-induced HCC in rats. Our in vivo study significantly revealed improvement in the liver-function biochemical markers (ALT, AST, GGT, and ALP), the tumor marker (AFP-L3), and the histopathological features of the treated groups. A UHPLC-Q-TOF-MS/MS analysis of the Ceiba pentandra ethyl acetate extract enabled the identification of fifty phytomolecules. Among these are the dietary flavonoids known to have anticancer, anti-inflammatory, and antioxidant qualities: protocatechuic acid, procyanidin B2, epicatechin, rutin, quercitrin, quercetin, kaempferol, naringenin, and apigenin. Our findings highlight C. pentandra as an affordable source of phytochemicals with possible chemosensitizing effects, which could be an intriguing candidate for the development of liver cancer therapy, particularly in combination with chemotherapeutic drugs.

A comparison of timing and patterns of treatment failure, and survival outcomes after progression between HPV+ and HPV- patients undergoing chemoradiation for oropharyngeal squamous cell carcinomas.

BACKGROUND: We aimed to analyze and compare the timing and patterns of treatment failure, and survival after progression between HPV-positive (HPV+) and HPV-negative (HPV-) patients undergoing chemoradiation for oropharyngeal squamous cell carcinomas (OPSCC). METHODS: A retrospective review was performed of all patients undergoing primary chemoradiation for OPSCC between 2008 and 2021. Demographic and clinical data were collected. Kaplan-Meier estimates for overall survival (OS), and time to recurrence/metastases (TTR) were compared using the log-rank test, with Cox regression used for multivariable modeling comparing HPV+ and HPV- patients. RESULTS: HPV- patients developed recurrence or metastases at earlier time points than HPV+ patients (8.8 vs. 15.2 months, p < 0.05), due to earlier local/locoregional recurrence and distant metastases, but not isolated regional recurrences. HPV- distant metastases exclusively occurred in a single organ, most commonly the lungs or bone, while HPV+ metastases frequently had multi-organ involvement in a wide variety of locations (p < 0.05). Once progression (recurrence/metastases) was diagnosed, HPV+ patients experienced superior survival to HPV- patients on univariate and multivariate analysis, largely due to improved outcomes after treatment of local/locoregional recurrences (p < 0.05). There were no differences in survival after isolated regional recurrences or distant metastases. CONCLUSION: HPV+ OPSCC patients relapse later compared to HPV- patients in local/locoregional and distant sites. HPV+ patients with local/locoregional recurrence experience superior survival after recurrence, which does not hold true for isolated regional recurrences or distant metastases. These data can be useful to inform prognosis and guide treatment decisions in patients with recurrent OPSCC.

Silver Nanoparticles Derived from Probiotic Lactobacillus casei-a Novel Approach for Combating Bacterial Infections and Cancer.

In the face of rising antibiotic resistance and the need for novel therapeutic approaches against cancer, the present study delves into the various facets of biosynthesized silver nanoparticles (AgNPs) derived from the probiotic strain Lactobacillus casei (AgNPs-LC), assessing their efficacy in combating bacterial infections, disrupting biofilm formation, interfering with quorum sensing mechanisms, and exhibiting anti-cancer properties. The results showed that the AgNPs-LC had a spherical shape with an average size of 15 nm. The biosynthesized AgNPs-LC showed a symmetrical absorption spectrum with a peak at 458 nm with a diameter of 5-20 nm. AgNPs-LC exhibited significant antibacterial activity against Gram-positive and Gram-negative bacteria and inhibited the biofilm formation (> 50% at sub-MIC) and quorum sensing-mediated virulence factors, such as the production of violacein in C. violaceum (> 80% at sub-MIC), pyocyanin in P. aeruginosa (> 70% at sub-MIC), and prodigiosin in S. marcescens (> 80% at sub-MIC). The exopolysaccharides (EPS) were also found to reduce in the presence of AgNPs-LC. Furthermore, the AgNPs-LC showed anti-cancer and anti-metastasis activity via inhibiting cell migration and invasion of human lung cancer (A-549) cells. Overall, the present study brings out the multifaceted therapeutic capabilities of AgNPs-LC which offer exciting prospects for the development of innovative biomedical and pharmaceutical interventions, making AgNPs-LC a versatile and promising candidate for a wide range of applications in healthcare and medicine. However, further research is essential to fully harness their therapeutic potential.

New Megastigmane and Polyphenolic Components of Henna Leaves and Their Tumor-Specific Cytotoxicity on Human Oral Squamous Carcinoma Cell Lines.

Polyphenols have a variety of phenolic hydroxyl and carbonyl functionalities that enable them to scavenge many oxidants, thereby preserving the human redox balance and preventing a number of oxidative stress-related chronic degenerative diseases. In our ongoing investigation of polyphenol-rich plants in search of novel molecules, we resumed the investigation of Lawsonia inermis L. (Lythraceae) or henna, a popular ancient plant with aesthetic and therapeutic benefits. The leaves' 70% aq acetone extract was fractionated on a Diaion HP-20 column with different ratios of H2O/an organic solvent. Multistep gel chromatographic fractionation and HPLC purification of the Diaion 75% aq MeOH and MeOH fractions led to a new compound (1) along with tannin-related metabolites, benzoic acid (2), benzyl 6'-O-galloyl-ß-D-glucopyranoside (3), and ellagic acid (4), which are first isolated from henna. Repeating the procedures on the Diaion 50% aq MeOH eluate led to the first-time isolation of two O-glucosidic ellagitannins, heterophylliin A (5), and gemin D (6), in addition to four known C-glycosidic ellagitannins, lythracin D (7), pedunculagin (8), flosin B (9), and lagerstroemin (10). The compound structures were determined through intensive spectroscopic investigations, including HRESIMS, 1D (1H and 13C) and 2D (1H-1H COSY, HSQC, HMBC, and NOESY) NMR, UV, [α]D, and CD experiments. The new structure of 1 was determined to be a megastigmane glucoside gallate; its biosynthesis from gallic acid and a ß-ionone, a degradative product of the common metabolite ß-carotin, was highlighted. Cytotoxicity investigations of the abundant ellagitannins revealed that lythracin D2 (7) and pedunculagin (8) are obviously more cytotoxic (tumor specificity = 2.3 and 2.8, respectively) toward oral squamous cell carcinoma cell lines (HSC-2, HSC-4, and Ca9-22) than normal human oral cells (HGF, HPC, and HPLF). In summary, Lawsonia inermis is a rich source of anti-oral cancer ellagitannins. Also, the several discovered polyphenolics highlighted here emphasize the numerous biological benefits of henna and encourage further clinical studies to profit from their antioxidant properties against oxidative stress-related disorders.

Prevalence of Sleep Disorders Among Patients With Type 2 Diabetes Mellitus at Primary Healthcare Centers in the South Region of Abha City.

Background Type 2 diabetes is a chronic condition that affects the way the body processes blood sugar (glucose). This issue is of considerable importance in the field of public health, as it has a global impact on a substantial number of individuals. The primary emphasis in the management of type 2 diabetes is centered around achieving glycemic control, implementing lifestyle adjustments, and employing pharmaceutical therapies as preventive measures or for the purpose of managing problems that may arise as a result of the disease. Aim This research aimed to investigate the prevalence of sleep-belated issues among individuals diagnosed with type 2 diabetes. Methodology A total of 230 participants with type 2 diabetes patients of primary healthcare in Abha city whose age is ≥18 years were included in the study. The data collection process involved the distribution of a self-administered questionnaire that assessed various aspects of sleep disturbances, including difficulties in falling asleep, waking up during the night, excessive daytime sleepiness, and restless legs or leg muscle cramps. The questionnaire also collected demographic information and data on potential risk factors such as alcohol consumption, caffeine consumption, and smoking/tobacco product use. Data analysis was conducted using chi-square tests and significance levels were set at p < 0.05. Results The findings revealed a prevalence of sleep disturbances among individuals with type 2 diabetes. Difficulties in falling asleep and waking up during the night were reported by a substantial proportion of participants, and a notable number experienced excessive daytime sleepiness. Restless legs or leg muscle cramps that interrupted sleep were experienced occasionally by 16.5% and frequently by 8.7% of the participants. The study also found a significant association between the presence of sleep problems and lower sleep quality ratings. However, no significant associations were found between sleep disturbances and the duration of type 2 diabetes or the examined risk factors. Conclusion The findings from this study emphasize the detrimental effects of sleep disturbances on sleep quality and suggest that improving sleep quality can positively influence the overall health and well-being of individuals with type 2 diabetes.

The antioxidant activity, preliminary phytochemical screening of Zingiber zerumbet and antimicrobial efficacy against selective endodontic bacteria.

Antibiotic resistance is rising across the world. For a very long time, bitter ginger (Zingiber zerumbet) has been used as one of the most popular herbal remedies to treat a wide range of common diseases. Ginger has been shown to have antioxidant and antibacterial activity. It has various bioactive chemicals that might be utilized as an alternative treatment option for many infectious diseases. The present study aimed to examine the biochemical profile of ginger, antioxidant, and antibacterial activity against selective endodontic microbes. Antioxidant was measured using DPPH and antibacterial activity was performed using disk diffusion tests. Streptococcus mutants, Enterococcus faecalis, Staphylococcus spp., and Lactobacillus spp. were tested for antibacterial activity. Before evaluating the dried extracts, all solvents were eliminated using rotary evaporation. The obtained IC50 value revealed that ethanol extract had the greatest antioxidant activity. Concerning each bacterium, the plant extracts demonstrated considerable antibacterial activity (p = .001). Ethanol extracts showed the strongest antibacterial activity against the studied microorganisms. This study highlights that the Zingiber zerumbet (Z. zerumbet) is a strong antibacterial herb against multidrug-resistant (MDR) gram-positive bacteria. It may also be employed as a possible natural antioxidant source.

Establishing the Role of Iridoids as Potential Kirsten Rat Sarcoma Viral Oncogene Homolog G12C Inhibitors Using Molecular Docking; Molecular Docking Simulation; Molecular Mechanics Poisson-Boltzmann Surface Area; Frontier Molecular Orbital Theory; Molecular Electrostatic Potential; and Absorption, Distribution, Metabolism, Excretion, and Toxicity Analysis.

The RAS gene family is one of the most frequently mutated oncogenes in human cancers. In KRAS, mutations of G12D and G12C are common. Here, 52 iridoids were selected and docked against 8AFB (KRAS G12C receptor) using Sotorasib as the standard. As per the docking interaction data, 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester (dock score: -9.9 kcal/mol), 6'-O-trans-para-coumaroyl geniposidic acid (dock score: -9.6 kcal/mol), 6-O-trans-cinnamoyl-secologanoside (dock score: -9.5 kcal/mol), Loganic acid 6'-O-beta-d-glucoside (dock score: -9.5 kcal/mol), 10-O-succinoylgeniposide (dock score: -9.4), Loganic acid (dock score: -9.4 kcal/mol), and Amphicoside (dock score: -9.2 kcal/mol) showed higher dock scores than standard Sotorasib (dock score: -9.1 kcal/mol). These common amino acid residues between iridoids and complexed ligands confirmed that all the iridoids perfectly docked within the receptor's active site. The 100 ns MD simulation data showed that RMSD, RMSF, radius of gyration, and SASA values were within range, with greater numbers of hydrogen bond donors and acceptors. MM/PBSA analysis showed maximum binding energy values of -7309 kJ/mol for 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester. FMO analysis showed that 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester was the most likely chemically reactive molecule. MEP analysis data highlighted the possible electrophilic and nucleophilic attack regions of the best-docked iridoids. Of all the best-docked iridoids, Loganic acid passed Lipinski, Pfizer, and GSK filters with a similar toxicity profile to Sotorasib. Thus, if we consider these iridoids to be KRAS G12C inhibitors, they will be a boon to mankind.

Analyzing Histological Images Using Hybrid Techniques for Early Detection of Multi-Class Breast Cancer Based on Fusion Features of CNN and Handcrafted.

Breast cancer is the second most common type of cancer among women, and it can threaten women's lives if it is not diagnosed early. There are many methods for detecting breast cancer, but they cannot distinguish between benign and malignant tumors. Therefore, a biopsy taken from the patient's abnormal tissue is an effective way to distinguish between malignant and benign breast cancer tumors. There are many challenges facing pathologists and experts in diagnosing breast cancer, including the addition of some medical fluids of various colors, the direction of the sample, the small number of doctors and their differing opinions. Thus, artificial intelligence techniques solve these challenges and help clinicians resolve their diagnostic differences. In this study, three techniques, each with three systems, were developed to diagnose multi and binary classes of breast cancer datasets and distinguish between benign and malignant types with 40× and 400× factors. The first technique for diagnosing a breast cancer dataset is using an artificial neural network (ANN) with selected features from VGG-19 and ResNet-18. The second technique for diagnosing breast cancer dataset is by ANN with combined features for VGG-19 and ResNet-18 before and after principal component analysis (PCA). The third technique for analyzing breast cancer dataset is by ANN with hybrid features. The hybrid features are a hybrid between VGG-19 and handcrafted; and a hybrid between ResNet-18 and handcrafted. The handcrafted features are mixed features extracted using Fuzzy color histogram (FCH), local binary pattern (LBP), discrete wavelet transform (DWT) and gray level co-occurrence matrix (GLCM) methods. With the multi classes data set, ANN with the hybrid features of the VGG-19 and handcrafted reached a precision of 95.86%, an accuracy of 97.3%, sensitivity of 96.75%, AUC of 99.37%, and specificity of 99.81% with images at magnification factor 400×. Whereas with the binary classes data set, ANN with the hybrid features of the VGG-19 and handcrafted reached a precision of 99.74%, an accuracy of 99.7%, sensitivity of 100%, AUC of 99.85%, and specificity of 100% with images at a magnification factor 400×.

Evaluation of the Wound Healing Potential of Cynara humilis Extracts in the Treatment of Skin Burns.

Cynara humilis is traditionally used to treat skin burns and microbial infections. However, experimental studies on this plant are rare. Furthermore, the aim of this study was to investigate the effects of Cynara humilis, a Moroccan herbal remedy, on the healing of deep second-degree burns in rats with a silver sulfadiazine group. This research was also carried out to confirm if C. humilis had antibacterial capabilities. Under typical burn procedures, each rat received a deep second-degree burn on the upper back. The burns were treated regularly with control groups (control and control VH), silver sulfadiazine (SDD) in group 3, C. humilis ethanolic extract (CHEE) in group 4, and C. humilis aqueous extract (CHAE) in group 5. Throughout the treatment, digital photography was used to measure rat responses to the treatment until day 18. After the scar biopsy at the end of the study, histological parameters (inflammatory cells, collagen, epithelialization, fibrosis, and granulation tissue) were assessed. Using the well technique, the antibacterial activity of the extracts was tested against Staphylococcus aureus CIP 483, Bacillus subtilis CIP 5262, Escherichia coli CIP 53126, Pseudomonas aeruginosa CIP 82118, and Salmonella enterica CIP 8039, and the results showed important activities of the ethanolic and aqueous extracts against the five species tested with MICs of 2 and 4 mg/mL, respectively. In the aqueous extract group, the wound healed faster. In addition, the healing rate in the C. humilis extracts (CHEA and CHEE) group was faster than in the silver sulfadiazine and control groups. In the C. humilis group, maximum wound surface recovery was observed at the same time, as it was not noted in the silver sulfadiazine group. Pathologically, epithelialization was more marked in wounds treated with C. humilis extracts (CHE). Angiogenesis and inflammatory cells were considerably lower in the CHE group than in the silver and other control groups. However, elastic fibers were considerable in the CHE-treated group. In histological examination, the C. humilis group had a low incidence of angiogenesis and inflammation, indicating that this group had less wound scarring. Collagen and burn wound healing were both faster in the C. humilis group. The findings of this study suggest that C. humilis, as indicated by traditional medicine, is a promising natural source for the management of wound healing.

Novel Glu-based pyrazolo[3,4-d]pyrimidine analogues: design, synthesis and biological evaluation as DHFR and TS dual inhibitors.

A novel series of multifunctional pyrazolo[3,4-d]pyrimidine-based glutamate analogs (6a-l and 7a,b) have been designed and synthesized as antifolate anticancer agents. Among the tested compounds, 6i exhibited the most potent anti-proliferative activity towards NSCLC, CNS, Ovarian, Prostate, Colon, Melanoma, Breast, and Renal cancers with good to weak cytostatic activity and non-lethal actions. 6i demonstrated higher selectivity for cancer than normal cells. 6i could significantly increase the accumulation of S-phase cells during the cell cycle distribution of cancer cells with high potency in the induction of apoptosis. The results unveiled that 6i probably acts through dual inhibition of DHFR and TS enzymes (IC50 = 2.41 and 8.88 µM, correspondingly). Docking studies of 6i displayed that N1-p-bromophenyl and C3-Methyl groups participate in substantial hydrophobic interactions. The drug-likeness features inferred that 6i met the acceptance criteria of Pfizer. Taking together, 6i could be a promising prototype for further optimization as an effective anticancer drug.

Histopathological Analysis for Detecting Lung and Colon Cancer Malignancies Using Hybrid Systems with Fused Features.

Lung and colon cancer are among humanity's most common and deadly cancers. In 2020, there were 4.19 million people diagnosed with lung and colon cancer, and more than 2.7 million died worldwide. Some people develop lung and colon cancer simultaneously due to smoking which causes lung cancer, leading to an abnormal diet, which also causes colon cancer. There are many techniques for diagnosing lung and colon cancer, most notably the biopsy technique and its analysis in laboratories. Due to the scarcity of health centers and medical staff, especially in developing countries. Moreover, manual diagnosis takes a long time and is subject to differing opinions of doctors. Thus, artificial intelligence techniques solve these challenges. In this study, three strategies were developed, each with two systems for early diagnosis of histological images of the LC25000 dataset. Histological images have been improved, and the contrast of affected areas has been increased. The GoogLeNet and VGG-19 models of all systems produced high dimensional features, so redundant and unnecessary features were removed to reduce high dimensionality and retain essential features by the PCA method. The first strategy for diagnosing the histological images of the LC25000 dataset by ANN uses crucial features of GoogLeNet and VGG-19 models separately. The second strategy uses ANN with the combined features of GoogLeNet and VGG-19. One system reduced dimensions and combined, while the other combined high features and then reduced high dimensions. The third strategy uses ANN with fusion features of CNN models (GoogLeNet and VGG-19) and handcrafted features. With the fusion features of VGG-19 and handcrafted features, the ANN reached a sensitivity of 99.85%, a precision of 100%, an accuracy of 99.64%, a specificity of 100%, and an AUC of 99.86%.