MicroRNAs as Potential Orchestrators of Alzheimer's Disease-Related Pathologies: Insights on Current Status and Future Possibilities.

Alzheimer's disease (AD) is a progressive and deleterious neurodegenerative disease, strongly affecting the cognitive functions and memory of seniors worldwide. Around 58% of the affected patients live in low and middle-income countries, with estimates of increasing deaths caused by AD in the coming decade. AD is a multifactor pathology. Mitochondrial function declines in AD brain and is currently emerging as a hallmark of this disease. It has been considered as one of the intracellular processes severely compromised in AD. Many mitochondrial parameters decline already during aging; mitochondrial efficiency for energy production, reactive oxygen species (ROS) metabolism and the de novo synthesis of pyrimidines, to reach an extensive functional failure, concomitant with the onset of neurodegenerative conditions. Besides its impact on cognitive functions, AD is characterized by loss of synapses, extracellular amyloid plaques composed of the amyloid-ß peptide (Aß), and intracellular aggregates of hyperphosphorylated Tau protein, accompanied by drastic sleep disorders, sensory function alterations and pain sensitization. Unfortunately, till date, effective management of AD-related disorders and early, non-invasive AD diagnostic markers are yet to be found. MicroRNAs (miRNAs) are small non-coding nucleic acids that regulate key signaling pathway(s) in various disease conditions. About 70% of experimentally detectable miRNAs are expressed in the brain where they regulate neurite outgrowth, dendritic spine morphology, and synaptic plasticity. Increasing studies suggest that miRNAs are intimately involved in synaptic function and specific signals during memory formation. This has been the pivotal key for considering miRNAs crucial molecules to be studied in AD. MicroRNAs dysfunctions are increasingly acknowledged as a pivotal contributor in AD via deregulating genes involved in AD pathogenesis. Moreover, miRNAs have been proved to control pain sensitization processes and regulate circadian clock system that affects the sleep process. Interestingly, the differential expression of miRNA panels implies their emerging potential as diagnostic AD biomarkers. In this review, we will present an updated analysis of miRNAs role in regulating signaling processes that are involved in AD-related pathologies. We will discuss the current challenges against wider use of miRNAs and the future promising capabilities of miRNAs as diagnostic and therapeutic means for better management of AD.

Lactoferrin-dual drug nanoconjugate: Synergistic anti-tumor efficacy of docetaxel and the NF-κB inhibitor celastrol.

Despite the progress in cancer nanotherapeutics, some obstacles still impede the success of nanocarriers and hinder their clinical translation. Low drug loading, premature drug release, off-target toxicity and multi-drug resistance are among the most difficult challenges. Lactoferrin (LF) has demonstrated a great tumor targeting capacity via its high binding affinity to low density lipoprotein (LDL) and transferrin (Tf) receptors overexpressed by various cancer cells. Herein, docetaxel (DTX) and celastrol (CST) could be successfully conjugated to LF backbone for synergistic breast cancer therapy. Most importantly, the conjugate self-assembled forming nanoparticles of 157.8 nm with elevated loading for both drugs (6.94 and 5.98% for DTX and CST, respectively) without risk of nanocarrier instability. Moreover, the nanoconjugate demonstrated enhanced in vivo anti-tumor efficacy in breast cancer-bearing mice, as reflected by a reduction in tumor volume, prolonged survival rate and significant suppression of NF-κB p65, TNF-α, COX-2 and Ki-67 expression levels compared to the group given free combined DTX/CST therapy and to positive control. This study demonstrated the proof-of-principle for dual drug coupling to LF as a versatile nanoplatform that could augment their synergistic anticancer efficacy.

Combination of magnetic targeting with synergistic inhibition of NF-κB and glutathione via micellar drug nanomedicine enhances its anti-tumor efficacy.

Breast cancer is not only one of the most prevalent types of cancer, but also it is a prime cause of death in women aged between 20 and 59. Although chemotherapy is the most common therapy approach, multiple side effects can result from lack of specificity and the use of overdose as safe doses may not completely cure cancer. Therefore, we aimed in this study is to combine the merits of NF-κB inhibiting potential of celastrol (CST) with glutathione inhibitory effect of sulfasalazine (SFZ) which prevents CST inactivation and thus enhances its anti-tumor activity. Inspired by the CD44-mediated tumor targeting effect of the hydrophilic polysaccharide chondroitin sulphate (ChS), we chemically synthesized amphiphilic zein-ChS micelles. While the water insoluble SFZ was chemically coupled to zein, CST was physically entrapped within the hydrophobic zein/SFZ micellar core. Moreover, physical encapsulation of oleic acid-capped SPIONs in the hydrophobic core of micelles enabled both magnetic tumor targeting as well as MRI theranostic capacity. Combining magnetic targeting to with the active targeting effect of ChS resulted in enhanced cellular internalization of the micelles in MCF-7 cancer cells and hence higher cytotoxic effect against MCF-7 and MDA-MB-231 breast cancer cells. In the in vivo experiments, magnetically-targeted micelles (154.4 nm) succeeded in achieving the lowest percentage increase in the tumor volume in tumor bearing mice, the highest percentage of tumor necrosis associated with significant reduction in the levels of TNF-α, Ki-67, NF-κB, VEGF, COX-2 markers compared to non-magnetically targeted micelles-, free drug-treated and positive control groups. Collectively, the developed magnetically targeted micelles pave the way for design of cancer nano-theranostic drug combinations.

Knowledge, attitudes, and practices of Sudanese residents towards COVID-19

Background: Coronavirus disease 2019 (COVID-19) is a severe acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sufficient knowledge, positive attitudes, and correct practices are crucial for the prevention of COVID-19. Aims: This study aimed at assessing the knowledge, attitudes and practices of a sample of Sudanese residents towards COVID-19. Methods: A cross-sectional community-based survey was conducted on 812 participants, including both sexes and aged 18 years and above, with the exclusion of health care workers. Considerable care was taken to include people with different education levels. Results: Among the survey respondents (n=812), 45.8% were women, 40.4% held a bachelor’s degree, 5.7% were uneducated, and 51.1% were aged 18-25 years. The overall correct rate of the knowledge questionnaire was 78.2%; 66.9% agreed that religious gatherings and events should be cancelled to prevent the spread of COVID-19; 34.1% of respondents wore medical masks; and 57.9% avoided shaking hands in recent days. Conclusion: This study showed that sampled Sudanese residents have incomplete knowledge and poor practices towards COVID-19. However, we found that women and people aged 18–25 years were more knowledgeable and had more positive attitudes towards COVID-19. We hope that concerned authorities will establish awareness programmes to improve the ability to combat this disease.

Pattern of oesophageal diseases in Madinah region, Saudi Arabia: An 11 years experience.

The oesophagus can be a site for a variety of lesions including inflammatory disorders, infections, mechanical conditions, toxic and physical injuries, vascular disorders and neoplastic conditions. hence the oesophageal diseases have a wide spectrum of pathological features. An understanding of histopathological details of oesophageal diseases is essential for their accurate diagnosis and management. The main objective of our study was to provide a comprehensive audit of oesophageal diseases in the province of Madinah in Saudi Arabia. From January 2006 to December 2017, were viewed the histopathological patterns of oesophageal lesions in patients at a tertiary care referral hospital who were diagnosed with oesophageal disease after upper gastroendoscopy. Of the 201 patients, 144 (71.6%) cases were found to be non-neoplastic and 57 (28.4%) cases were neoplastic. Our findings were comparable with earlier studies that helped establish a baseline of an oesophageal disease pattern, on the basis of histopathological examinations.

Dual-Targeted Lactoferrin Shell-Oily Core Nanocapsules for Synergistic Targeted/Herbal Therapy of Hepatocellular Carcinoma.

Herein, both strategies of synergistic drug combination together with dual active tumor targeting were combined for effective therapy of hepatocellular carcinoma (HCC). Therefore, based on the tumor sensitizing action, the herbal quercetin (QRC) was co-delivered with the targeted therapeutic drug sorafenib (SFB), preformulated as phospholipid complex, via protein shell-oily core nanocapsules (NCs). Inspired by the targeting action of lactoferrin (LF) via binding to LF receptors overexpressed by HCC cells, LF shell was electrostatically deposited onto the drug-loaded oily core to elaborate LF shell-oily core NCs. For dual tumor targeting, lactobionic acid (LA) or glycyrrhetinic acid (GA) was individually coupled to LF shell for binding to asialoglycoprotein and GA receptors on liver cancer cells, respectively. Compared to LF and GA/LF NCs, the dual-targeted LA/LF-NCs showed higher internalization into HepG2 cells with 2-fold reduction in half-maximal inhibitory concentration compared to free combination therapy after 48 h. Moreover, dual-targeted LF-NCs showed powerful in vivo antitumor efficacy. It was revealed as significant downregulation of the mRNA expression levels of nuclear factor-kappa B and tumor necrosis factor α as well as suppression of Ki-67 protein expression level in diethylnitrosamine (DEN)-induced HCC mice (P < 0.05). Furthermore, dual-targeted LF-NCs attenuated the liver toxicity induced by DEN in animal models. Overall, this study proposes dual-targeted LF-NCs for combined delivery of SFB and QRC as a potential therapeutic HCC strategy.

Metaplastic squamous cell carcinoma of breast. A pathology case report with review of literature.

Metaplastic Breast Carcinoma (MBC) is a group of rare breast cancers; squamous cell carcinoma (SCC) is its most common member. Due to rarity of the condition, frequent case reports have been published of late. In the last one year alone, there were about a dozen such reports. Here we report a case of primary squamous cell carcinomain a 62-year-old female, with a 3.5cm mass in the left breast. Biopsy and mastectomy reports confirmed Metaplastic carcinoma, with 21 benign lymph nodes.. The tumour was triple negative and cytokeratin 5/6 positive. We are reporting the first case of squamous cell carcinoma of breast from our region, and we recommended large multi centre studies.