Dr Mohammed Mahmoud Youssif

BACKGROUND AND AIM: infections in lactating buffaloes pose significant health and economic challenges due to maternal transmission of inhibited larvae to calves via colostrum and milk. This study aimed to identify species morphologically and genetically and to evaluate a novel strategic treatment using fenbendazole to suppress larval transmission.

MATERIALS AND METHODS: Morphological and genetic characterization of species was performed using light and scanning electron microscopy and mitochondrial gene analysis. Pregnant buffaloes previously infected with were administered fenbendazole (10 mg/kg body weight) 15 days before parturition (dbp). The animals were divided into three groups based on the interval between treatment and parturition: 6 days (G-1), 10 days (G-2), and 15 days (G-3). Colostrum, milk, and fecal samples were collected to assess larval and egg counts, respectively.

RESULTS: The genetic analysis confirmed the species as with 100% nucleotide similarity to reference sequences. The treatment effectively suppressed larval transmission in G-1, with no larvae detected in colostrum or milk, and significantly reduced larval counts in G-2 and G-3. Fecal egg counts of treated buffaloes and their calves were markedly lower than untreated controls. Statistically significant reductions in worm burden were observed, particularly in the group treated 6 dbp.

CONCLUSION: A single dose of fenbendazole administered 6 dbp effectively interrupted the transmission cycle, reducing larval presence in colostrum and milk and minimizing worm burdens in buffaloes and calves. Morphological and molecular analyses highlighted the efficacy of gene markers in species identification and phylogenetic studies. This strategic intervention represents a practical approach to controlling infections, improving herd health, and reducing environmental contamination.

The opportunistic pathogen Acinetobacter baumannii is a particularly problematic nosocomial threat worldwide, leading to high morbidity and mortality rates due to its multiple resistance mechanisms, including the production of lipolytic enzymes. Herein, the aerial parts of three coniferous plants, Pinus canariensis C. Sm. (PC), Cupressus lusitanica Mill. (CL), and Cupressus arizonica Greene. (CA), were extracted and fractionated. Among these, the CA extract followed by CL and then PC, exhibited the highest inhibition of bacterial lipase activity, with half-maximal inhibitory concentration (IC) values of 1117 ± 87, 1278 ± 62, and 1926 ± 104 µg/mL, respectively. The methylene chloride fractions of CA and CL extracts exhibited the highest inhibition of bacterial lipase activity, with IC (940 ± 25 µg/mL and 1103 ± 155 µg/mL), respectively. The metabolite profile of the three extracts, along with their most active fractions, were determined using liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). Interestingly, the metabolite profiles of CL extracts were established here for the first time. A total of 99 secondary metabolites from diverse classes were identified across all samples. Among these, four metabolites were isolated: 3,5-di-p-coumaroylquinic acid, epicatechin, cupressuflavone, and rutin. The biflavonoid cupressuflavone showed the lowest IC value (3812 ± 450 µg/mL). Additionally, partial least squares was applied to assess the key metabolites contributing to the differentiation of the studied bioactivity. Consequently, this study provides novel insights into the bioactivity potential of coniferous plants, demonstrating their value as a natural source of antivirulence agents against the A. baumannii lipase enzyme.

About one-third of renal cell carcinoma (RCC) patients present with metastatic disease upon diagnosis because of the retroperitoneal location of the kidneys, which causes many tumors to stay asymptomatic. Besides, shortly after 5 years following successful curative surgery, nearly 30% of individuals develop distant cancer metastases and recurrences. This is mostly attributable to the complex and diverse characteristics of the tumor microenvironment. Although targeted treatments and immunotherapies can extend the survival of patients, they are linked to the swift emergence of resistance, constraining the therapeutic alternatives for RCC patients and drawing attention to the critical requirement for improved targeted treatments. Along the same vein, there is an urgent demand for novel biomarkers capable of detecting early RCC with significant sensitivity and specificity. Additionally, prognostic indicators are required for the stratification of RCC patients. MicroRNAs (miRNAs) are crucial regulators of mRNA and subsequent protein production in both healthy and malignant tissues. The malignant pathophysiology of RCC has been associated with miRNA dysregulation, which impacts numerous cellular processes and has been found to increase the likelihood of proliferative and invasive processes, promote angiogenesis, alter cell cycle dynamics, evade cell death, facilitate metastasis, and make cancer cells less responsive to certain treatments. Therefore, in this review, we will go over the latest findings regarding the functions of oncogenic and tumor suppressor miRNAs in RCC, how they could be used as diagnostic and prognostic indicators for RCC, and the role they play in the development of RCC and its resistance to cancer-fighting therapies.

Colorectal cancer (CRC) is the third most prevalent cancer worldwide. While chemotherapy remains the standard treatment approach, natural products have emerged as a promising alternative. Among these, apigenin, a natural flavonoid, has garnered significant attention due to its pro-oxidant and antioxidant properties in various types of cancer. This study aimed to assess the potential impact of apigenin in CRC treatment by targeting mitochondrial SIRT3, HMGB1, and beclin 1-mediated autophagy in a mouse model of CRC. We administered 20 mg/kg of dimethyl hydrazine (DMH) intraperitoneally once weekly for 20 weeks to induce CRC in C57BL/6 mice. After 6 weeks of initiating the study, apigenin was intragastrically co-administered by oral gavage at 25 and 50 mg/kg until the end of week 20. The results revealed significant weight loss, shortening of the colon, and diarrhea in DMH-induced CRC, which are considered the marks of CRC. In addition, histopathological examination revealed dysplastic changes in the DMH-treated group, while no dysplasia was found in the apigenin-treated CRC groups. Importantly, the administration of apigenin to DMH-treated animals has led to a significant reduction of SIRT3 and MnSOD expression levels with a significant increase in LC3-II at either dose and a significant dose-dependent increase in the levels of MDA, c-JNK, HMGB1, and beclin 1 compared to the DMH-treated group. In conclusion, apigenin may have a promising role in suppressing DMH-induced CRC. It elicits a pro-oxidant activity by suppressing the gene expression of SIRT3 and subsequently, its target MnSOD, resulting in increased reactive oxygen species (ROS) and lipid peroxidation. The released ROS, in turn, activates JNK-mediated autophagy by enhancing HMGB1, beclin 1, and LC3-II protein levels.

Herein, we investigated the preparation and characterization of Terconazole loaded edge-activated hybrid elastosome (TCN-EHE) adopting thin film hydration technique for the treatment of ocular mycosis. Terconazole (TCN) is a broad spectrum antimycotic agent suffering from sparse aqueous solubility impeding its use in ophthalmic preparations. The scrutinized formulation variables namely X: Surfactant: Edge activator ratio (SAA: EA), X: Pluronic® L121 contribution (% of total SAA) and X: EA concentration (%/) were optimized adopting D-optimal design. Ten runs were prepared and characterized regarding their entrapment efficiency, particle size, polydispersity index and zeta potential. An optimized formula was generated, with high desirability, exhibited satisfactory entrapment efficiency, nanoscaled particle size aligning with TEM, plausible zeta potential and bi-phasic release pattern which were not altered after short-term storage. The optimized TCN-EHE displayed 1.94-fold enhanced ex-vivo corneal permeation flux. Safety was ratified through measured corneal hydration level, pH and histopathological evaluation. In-vivo corneal uptake visualized by confocal laser microscopy demonstrated 2.7-fold deeper penetration. Moreover, Superior antifungal activity has been demonstrated displaying 37 % bigger zone of inhibition, 8-fold lower minimum inhibitory and minimum fungal concentration alongside significantly higher biofilm inhibition activity at all tested concentrations for the optimized TCN-EHE compared to TCN suspension. Conclusively, we could prospect that TCN-EHE might be a revamped therapeutic alternative for the delivery of poorly soluble antimycotic agents for the combat of ocular mycosis.

Shogaol, a significant bioactive constituent of ginger, is present in several forms, including 4-, 6-, 8-, 10-, and 12-shogaol, with 6-shogaol identified as the most potent among them. Notably, 6-shogaol can be metabolized into 6-paradol, a compound that lacks pungency but retains biological activity. The primary focus of this review is to trace the diverse pharmacological effects of 6-shogaol, such as its anti-inflammatory, cardioprotective, neuroprotective, antioxidant, and anticancer properties, and to document the molecular mechanisms underlying these actions. 6-Shogaol's broad spectrum of benefits makes it valuable in the health, food, and beverage industries, where its unique taste, high biocompatibility, and ability to alleviate or prevent various health issues are particularly advantageous. Its multiple mechanisms of action, including the modulation of oxidative stress and inflammation, contribute to its reputation as a promising natural compound. By highlighting the therapeutic potential of 6-shogaol, this review aims to provide a scientific foundation for its future development, clinical application, and incorporation into functional foods or pharmaceuticals, ultimately supporting its role as a versatile agent in promoting human health.