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Khaled S Allemailem,1,2 Ahmad Almatroudi,1 Faris Alrumaihi,1 Saleh A Almatroodi,1 Mohammad O Alkurbi,3 Ghaiyda Talal Basfar,3 Arshad Husain Rahmani,1 Amjad Ali Khan2 1Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia; 2Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia; 3Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi ArabiaCorrespondence: Amjad Ali KhanDepartment of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, P.O. Box 6699, Buraydah, 51452, Saudi ArabiaTel +966-16-3800050 Ext. 15445Fax +96616 3801628Email akhan@qu.edu.saAbstract: The smart strategy of cancer cells to bypass the caspase-dependent apoptotic pathway has led to the discovery of novel anti-cancer approaches including the targeting of lysosomes. Recent discoveries observed that lysosomes perform far beyond just recycling of cellular waste, as these organelles are metabolically very active and mediate several signalling pathways to sense the cellular metabolic status. These organelles also play a significant role in mediating the immune system functions. Thus, direct or indirect lysosome-targeting with different drugs can be considered a novel therapeutic approach in different disease including cancer. Recently, some anticancer lysosomotropic drugs (eg, nortriptyline, siramesine, desipramine) and their nanoformulations have been engineered to specifically accumulate within these organelles. These drugs can enhance lysosome membrane permeabilization (LMP) or disrupt the activity of resident enzymes and protein complexes, like v-ATPase and mTORC1. Other anticancer drugs like doxorubicin, quinacrine, chloroquine and DQ661 have also been used which act through multi-target points. In addition, autophagy inhibitors, ferroptosis inducers and fluorescent probes have also been used as novel theranostic agents. Several lysosome-specific drug nanoformulations like mixed charge and peptide conjugated gold nanoparticles (AuNPs), Au-ZnO hybrid NPs, TPP-PEG-biotin NPs, octadecyl-rhodamine-B and cationic liposomes, etc. have been synthesized by diverse methods. These nanoformulations can target cathepsins, glucose-regulated protein 78, or other lysosome specific proteins in different cancers. The specific targeting of cancer cell lysosomes with drug nanoformulations is quite recent and faces tremendous challenges like toxicity concerns to normal tissues, which may be resolved in future research. The anticancer applications of these nanoformulations have led them up to various stages of clinical trials. Here in this review article, we present the recent updates about the lysosome ultrastructure, its cross-talk with other organelles, and the novel strategies of targeting this organelle in tumor cells as a recent innovative approach of cancer management.Keywords: lysosome, cancer, lysosomotropic agents, nanoparticles, lysosome drug targeting

Abstract Background Phlebotomine insects harbor bacterial, viral and parasitic pathogens that can cause diseases of public health importance. Lutzomyia longipalpis is the main vector of visceral leishmaniasis in the New World. Insects can mount a powerful innate immune response to pathogens. Defensin peptides take part in this response and are known to be active against Gram-positive and Gram-negative bacteria, and some parasites. We studied the expression of a defensin gene from Lutzomyia longipalpis to understand its role in sand fly immune response. Methods We identified, sequenced and evaluated the expression of a L. longipalpis defensin gene by semi-quantitative RT-PCR. The gene sequence was compared to other vectors defensins and expression was determined along developmental stages and after exposure of adult female L. longipalpis to bacteria and Leishmania. Results Phylogenetic analysis showed that the L. longipalpis defensin is closely related to a defensin from the Old World sand fly Phlebotomus duboscqi. Expression was high in late L4 larvae and pupae in comparison to early larval stages and newly emerged flies. Defensin expression was modulated by oral infection with bacteria. The Gram-positive Micrococcus luteus induced early high defensin expression, whilst the Gram-negative entomopathogenic Serratia marcescens induced a later response. Bacterial injection also induced defensin expression in adult insects. Female sand flies infected orally with Leishmania mexicana showed no significant difference in defensin expression compared to blood fed insects apart from a lower defensin expression 5 days post Leishmania infection. When Leishmania was introduced into the hemolymph by injection there was no induction of defensin expression until 72 h later. Conclusions Our results suggest that L. longipalpis modulates defensin expression upon bacterial and Leishmania infection, with patterns of expression that are distinct among bacterial species and routes of infection.

Schistosomiasis, which affects a large number of people worldwide, is among the most overlooked parasitic diseases. The disease is mainly prevalent in sub-Saharan Africa, southeast Asian countries, and South America due to the lack of adequate sanitation. The disease is mainly associated with poor hygiene, sanitation, and contaminated water, so it is also known as a disease of poverty. Three Schistosoma species ( S. mansoni , S. japonicum , and S. haematobium ) cause significant human infections. Co-infections with Schistosoma and other parasites are widely common. All these parasites may cause intestinal or urogenital schistosomiasis, where the disease may be categorized into the acute, sensitized, and chronic phases. The disease is more prevalent among school children, which may cause anemia and reduce development. Chronic infections frequently cause significant liver, intestinal, and bladder damage. Women exposed to contaminated water while performing normal duties like washing clothes might acquire urogenital schistosomiasis (UGS), which can cause tissue damage and raise the risk of blood-borne disease transmission, including human immunodeficiency virus (HIV) transmission. Praziquantel (PZQ) is the World Health Organization (WHO)-prescribed treatment for individuals who are known to be infected, but it does not prevent further re-infections with larval worms. Vaccine development and new molecular-based diagnosis techniques have promised to be a reliable approach to the diagnosis and prevention of schistosomiasis. The current review emphasizes the recent advancement in the diagnosis of schistosomiasis by molecular techniques and the treatment of schistosomiasis by combined and alternative regimes of drugs. Moreover, this review has also focused on the recent outbreak of schistosomiasis, the development of vaccines, and their clinical trials.

Malaria infection still represents a notable public health risk in Saudi Arabia. This cross-sectional study aimed to determine the prevalence of Plasmodium species among clinically suspected cases who presented at Badr General Hospital and healthcare facilities in selected regions of Badr Governorate, Madinah Province, Saudi Arabia between January 2021 and January 2022. A total of 493 suspected patients were recruited from Badr Governorate, investigated for malaria infection using CBFME and rapid diagnostic test- CareStart Malaria Pf/PAN (HRP2/pLDH) Ag Combo rapid diagnostic tests. The results showed that malaria infection was 34 (6.89%) cases among 493 suspected patients using microscopic examination as reference test. Moreover, subjects aged 31 to 40 years and those aged 51 to 60 years had the highest (50%) and lowest (8.82%) percentages of malaria cases. Plasmodium vivax (19/34, 55.88%) was higher than P falciparum (15/34, 44.1%) as the causative agents of malaria cases. The majority of malaria cases (29/34, 80.9%) among non-Saudi mainly from Sudan (15/34, 44.1%), Pakistan (5/34, 14.7%), Bangladesh (5/34, 14.7%) and India (4/34, 11.76%) whereas malaria cases among Saudis (5/34, 14.7%). In addition, the majority of malaria cases (32/34, 94.11%) among male subjects while (2/34, 5.88%) among females. The current study revealed that malaria transmission is still active in Badr Governorate, Madinah Province, Saudi Arabia and represents a public health concern. Further screening implements and continuous epidemiological monitor of the status of malaria infection in Kingdom of Saudi Arabia are thus warranted to improve its controlling activities and eradicate malaria endemicity in the country., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study aimed to investigate the relationship between gastrointestinal tract infection and dengue hemorrhagic fever. Dengue hemorrhagic fever is a syndrome caused by the dengue virus and primarily affects children below ten years of age and is spread by the Aedes aegypti mosquito. Gastrointestinal tract infection is a bacterial and parasitic infection that leads to gastrointestinal tract inflammation which involves the small intestine and the stomach. The relationship between the two can be manifested by gastrointestinal bleeding, acute pancreatitis, and fulminant liver failure. In this research work, 600 blood and feces samples of different ages and sex (7-8 worms) were collected from Jeddah city. From the blood samples, serum was made and stored at -20°C until use. The frozen sera samples were investigated for sero-detection of DENV-NS1 antigen as a rapid, sensitive, and cost-effective test to detect asymptomatic acute DENV-infected donors and anti-DENV IgM and IgG antibodies. Feces samples were processed for the detection of parasites. The data acquired from these samples of all the 600 participants were analyzed and interpreted, followed by statistical analysis using GraphPad Prism 5.0 software. All the values were considered significant, which showed a value of less than 0.05. Results were expressed as with the range. This article documents that gastrointestinal tract manifestations frequently occur among patients with dengue hemorrhagic fever. There are close relationships between gastrointestinal tract infection and dengue hemorrhagic fever. In current work, it was established that dengue fever leads to gastrointestinal tract bleeding in the presence of intestinal parasites. Therefore, failure to identify the patients with this infection early enough can lead to an increased morbidity and mortality rate.

Introduction: toxoplasmosis is an opportunistic protozoan disease caused by Toxoplasma gondii (T. gondii) infection. It affects all human ages, including children, and can pose serious health problems, particularly in developing countries. Nevertheless, the epidemiological status of neonatal and childhood toxoplasmosis remains largely unknown in Saudi Arabia. The present study aimed to determine the seroprevalence of T. gondii infection among Saudi babies residing in Jeddah Region of Saudi Arabia., Methods: this hospital-based retrospective study was conducted between January 2019 and March 2021 at three governmental hospitals in Jeddah Region: King Fahad, King Abdulaziz, and East Jeddah Hospital. It included 502 babies (269 boys and 233 girls; 0-4 years old), who were screened by enzyme linked immunosorbent assay (ELISA) for the detection of anti-T. gondii immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies in their serum., Results: among the 502 studied babies, the overall seropositivity rate of T. gondii infection was 18.53% (93/502) subscribed as 90 babies (17.9%) with IgG seropositive and 3 babies (0.60%) with IgM seropositivity. The all IgG seropositive babies were IgM seronegative and vice versa. Additionally, the highest proportion of IgG seropositivity was detected in 0-6 month old babies (7.17%); followed by 5.38% and 4.98% in 7-12 and 13-18 months old babies, respectively, while the 3 babies with IgM seropositivity were 13-18 months old., Conclusion: the present findings highlighted the seroprevalence situation of toxoplasma infection among babies in some Saudi communities and raise the importance to increase the screening programs and preventative implements against toxoplasmosis in Saudi Arabia., Competing Interests: The authors declare no competing interest., (Copyright: Raafat Abdel Moneim Hassanein et al.)

The basis of severe malaria pathogenesis in part includes sequestration of Plasmodium falciparum-infected erythrocytes (IE) from the peripheral circulation. This phenomenon is mediated by the interaction between several endothelial receptors and one of the main parasite-derived variant antigens (PfEMP1) expressed on the surface of the infected erythrocyte membrane. One of the commonly used host receptors is ICAM-1, and it has been suggested that ICAM-1 has a role in cerebral malaria pathology, although the evidence to support this is not conclusive. The current study examined the cytoadherence patterns of lab-adapted patient isolates after selecting on ICAM-1. We investigated the binding phenotypes using variant ICAM-1 proteins including ICAM-1Ref, ICAM-1Kilifi, ICAM-1S22/A, ICAM-1L42/A and ICAM-1L44/A using static assays. The study also examined ICAM-1 blocking by four anti-ICAM-1 monoclonal antibodies (mAb) under static conditions. We also characterised the binding phenotypes using Human Dermal Microvascular Endothelial Cells (HDMEC) under flow conditions. The results show that different isolates have variant-specific binding phenotypes under both static and flow conditions, extending our previous observations that this variation might be due to variable contact residues on ICAM-1 being used by different parasite PfEMP1 variants.