Hematologic malignancies, which arise from dysregulation of hematopoiesis, are a group of cancers originating in cells with diminished capacity to differentiate into mature progeny and accumulating immature cells in blood-forming tissues such as lymph nodes and bone marrow. Immune- targeted therapies, such as Immune Checkpoint Blockade (ICB), chimeric antigen receptor T (CAR-T) cell therapy, and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system, a precise, popular, and versatile genome engineering tool, have opened new avenues for the treatment of malignancies. Targeting immune checkpoints has revolutionized FDA approval in cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), PD-1 (programmed death-1), and PDL1. According to the ICB and CAR techniques, the production of efficient CAR-T cells depends on the successful genetic modification of T cells, making them less susceptible to immune escape and suppression by cancer cells, which results in reduced off-target toxicity. Therefore, CRISPR/Cas9 has revolutionized the immune checkpoint-based approach for CAR-T cell therapy of hematologic malignancy. Continued research and clinical trials will undoubtedly pave the way for further advances in this field, ultimately benefiting patients and improving outcomes.

Background and Objective: Associations between probiotics as dietary supplements for health enhancement and illness management and human health include a long history. Currently, probiotics represent a potential category of microorganisms used in the development of oral vaccines for the treatment of allergies, infectious diseases, and cancers. The vaccine promises as safe therapeutic options, their capacity to elicit mucosal and systemic immune responses, and their cost-effectiveness resulting from the absence of complex purification processes have been addressed. Results and Conclusion: Despite the advantages of probiotics as oral vaccines, their uses still include problems such as inadequate targeted colonization, diminished immune response in populations with low hygiene standards, reliance on individual microbiota, poor stability, limited efficacy, and absence of targeted immunogenicity. To address these problems, probiotics can be engineered using gene editing technologies, particularly CRISPR/Cas system. Concerns are reported regarding the safety of genetic alterations and deficiencies in efficient delivery mechanisms linked to the use of modified probiotics as oral vaccines. Further studies are needed to assess problems associated with accurate genetic alteration and efficient delivery methods to achieve the ultimate goal of further effective and safer vaccinations.

Undoubtedly, mesenchymal stem cells (MSCs) are the most common cell therapy candidates in clinical research and therapy. They not only exert considerable therapeutic effects to alleviate inflammation and promote regeneration, but also show low-immunogenicity properties, which ensure their safety following allogeneic transplantation. Thanks to the necessity of providing a sufficient number of MSCs to achieve clinically efficient outcomes, prolonged in vitro cultivation is indisputable. However, either following long-term in vitro expansion or aging in elderly individuals, MSCs face cellular senescence. Senescent MSCs undergo an impairment in their function and therapeutic capacities and secrete degenerative factors which negatively affect young MSCs. To this end, designing novel investigations to further elucidate cellular senescence and to pave the way toward finding new strategies to reverse senescence is highly demanded. In this review, we will concisely discuss current progress on the detailed mechanisms of MSC senescence and various inflicted changes following aging in MSC. We will also shed light on the examined strategies underlying monitoring and reversing senescence in MSCs to bypass the comprised therapeutic efficacy of the senescent MSCs.

Celiac disease (CD) is a chronic autoimmune enteropathy and multifactorial disease caused by inappropriate immune responses to gluten in the small intestine. Weight loss, anemia, osteoporosis, arthritis, and hepatitis are among the extraintestinal manifestations of active CD. Currently, a strict lifelong gluten-free diet (GFD) is the only safe, effective, and available treatment. Despite the social burden, high expenses, and challenges of following a GFD, 2 to 5 percent of patients do not demonstrate clinical or pathophysiological improvement. Therefore, we need novel and alternative therapeutic approaches for patients. Innovative approaches encompass a broad spectrum of strategies, including enzymatic degradation of gluten, inhibition of intestinal permeability, modulation of the immune response, inhibition of the transglutaminase 2 (TG2) enzyme, blocking antigen presentation by HLA-DQ2/8, and induction of tolerance. Hence, this review is focused on comprehensive therapeutic strategies ranging from dietary approaches to novel methods such as antigen-based immunotherapy, cell and gene therapy, and the usage of nanoparticles for CD treatment.

Urological symptoms are usually accompanied by several etiologies; therefore, diagnosis is often based on multiple tests, which include imaging and urine analysis, among others. One of the most frequent causes of sharp pain in the population is kidney stones, which usually develop in the renal system. It would be possible to determine the levels of kidney stones appropriately by analyzing the size distribution of substances, such as crystals, in a urine sample. These polyester mesh filters in microfluidic devices represent the state-of-the-art solution in rapid and precise crystal isolation and identification. In the present study, we are presenting a centrifugal microfluidic platform for such an application. The proposed system uses centrifugal force to drive the urine sample through mesh filters of selectable pore sizes. Employing an innovative valving strategy, a backwash step enables the retrograde flow of washing liquid to displace trapped larger particles into a dedicated detection chamber. The introduced backwash process represents the foremost advantage of this microfluidics-based filtration device, facilitating high-resolution trapping of particles of specific sizes. Furthermore, the system boasts user-friendly operation and affordability. Experimental results demonstrate the system’s capability to effectively filter particles larger than 15 µm from heterogeneous samples in under 5 min. Optimization of disc rotational velocity ensures optimal liquid discharge timing and particle retrieval. Subsequently, we apply the system to the filtration of crystals from urine samples. Image processing of specimens within collection chambers underscores the technique’s proficiency in classifying crystals within samples into normal and high-risk categories.

Mesenchymal stem cells (MSCs), as self-renewing multipotent stromal cells, have been considered promising agents for cancer treatment. A large number of studies have demonstrated the valuable properties of MSC-based treatment, such as low immunogenicity and intrinsic tumor-trophic migratory properties. To enhance the potency of MSCs for therapeutic purposes, equipping MSCs with targeted delivery functions using genetic engineering is highly beneficial. Genetically engineered MSCs can express tumor suppressor agents such as pro-apoptotic, anti-proliferative, anti-angiogenic factors and act as ideal delivery vehicles. MSCs can also be loaded with nanoparticle drugs for increased efficacy and externally moderated targeting. Moreover, exosomes secreted by MSCs have important physiological properties, so they can contribute to intercellular communication and transfer cargo into targeted tumor cells. The precise role of genetically modified MSCs in tumor environments is still up for debate, but the beginning of clinical trials has been confirmed by promising results from preclinical investigations of MSC-based gene therapy for a wide range of malignancies. This review highlights the advanced techniques of engineering/nano-engineering and MSC-derived exosomes in tumor-targeted therapy.

BACKGROUND:Chinese hamster ovary (CHO) cells are the most predominantly utilized host for the production of monoclonal antibodies (mAbs) and other complex glycoproteins. A major challenge in the process of CHO cell culture is the occurrence of cell death following different stressful conditions, which hinders the production yield. Engineering genes involved in pathways related to cell death is a remarkable strategy to delay apoptosis, improve cell viability and enhance productivity. SIRT6 is a stress-responsive protein that regulates DNA repair, maintains genome integrity, and is critical for longevity and cell survival in organisms.METHODS AND RESULTS:In this study, SIRT6 was stably overexpressed in CHO-K1 cells and the impact of its expression on apoptosis related gene expression profile, viability, apoptosis, and mAb productivity was investigated. While a significant increase was observed in Bcl-2 mRNA level, caspase-3 and Bax mRNA levels were decreased in the SIRT6 engineered cells compared to the parental CHO-K1 cells. Moreover, improved cell viability and decreased rate of apoptotic progression was observed in a SIRT6-derived clone in comparision to the CHO-K1 cells during 5 days of batch culture. anti-CD52 IgG1 mAb titers were improved up to 1.7- and 2.8-fold in SIRT6-derived clone during transient and stable expression, respectively.CONCLUSIONS:This study indicates the positive effects of SIRT6 overexpression on cell viability and anti-CD52 IgG1 mAb expression in CHO-K1 cells. Further studies are needed to examine the potential of SIRT6-engineered host cells for the production of recombinant biotherapeutics in industrial settings.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia and joint damage. Systemic complications and progressive disability are burdens that lead to a significant socio-economic costs in patients with RA. Current RA biomarkers used in predicting, diagnosing, and monitoring the treatment of the disease have not been very successful. Moreover, only 60% of patients show a satisfactory response to current biological and conventional therapies. Studies on immunometabolism have suggested that dysregulated enzymes, transcription factors, metabolites, and metabolic pathways could be considered potential therapeutic targets for the treatment of RA. Factors such as the high concentration of various intermediate molecules arising from metabolism, hypoxia, lack of nutrients, and other metabolic alterations affect local immune responses and preserve a state of chronic inflammation in synovial tissues. Fortunately, in vitro and in vivo studies have shown that targeting specific metabolic pathways is associated with a decreased level of inflammation. Specifically, targeting metabolic intermediates, such as succinate or lactate, has shown promising clinical outcomes in RA treatment. These findings open an avenue for the identification of novel biomarkers for diagnosis, prognosis, and determining the success of various treatments in RA patients, as well as the discovery of new therapeutic targets.

Alzheimer's disease, a progressive neurological condition, is associated with various internal and external risk factors in the disease's early stages. Early diagnosis of Alzheimer's disease is essential for treatment management. Circulating exosomal microRNAs could be a new class of valuable biomarkers for early Alzheimer's disease diagnosis. Different kinds of biosensors have been introduced in recent years for the detection of these valuable biomarkers. Isolation of the exosomes is a crucial step in the detection process which is traditionally carried out by multi-step ultrafiltration. Microfluidics has improved the efficiency and costs of exosome isolation by implementing various effects and forces on the nano and microparticles in the microchannels. This paper reviews recent advancements in detecting Alzheimer's disease related exosomal microRNAs based on methods such as electrochemical, fluorescent, and SPR. The presented devices' pros and cons and their efficiencies compared with the gold standard methods are reported. Moreover, the application of microfluidic devices to detect Alzheimer's disease related biomarkers is summarized and presented. Finally, some challenges with the performance of novel technologies for isolating and detecting exosomal microRNAs are addressed.

Abstract The debate on Islam and human rights is roughly 50 years old. During this time a vast literature has been produced analyzing the relationship between the religion of Islam, Muslims societies and international human rights norms. What have we learned during this time that can further an understanding of this topic among students, scholars and members of the general public? What analytical framework is optimal? Is the crisis of human rights in Muslims societies a function of internal conditions, external factors or are they to be located within the framework of Islamic doctrine, traditions, the shariah in particular? This article grapples with these questions by looking back over the past five decades. The objective of this essay is to advance an objective framework of analysis for understanding the debate on Islam and human rights. A historical and comparative approach is adopted. Key moments that have shaped the debate on Islam and human rights are recalled. Significant political developments that have shaped the contours of the debate are examined such as the legacy of colonialism, the rise of political Islam, the role of Western policy and the failure of the post-colonial state in the Arab-Islamic world. The contributions of influential scholars and activists who have advanced the struggle for human rights in Muslims societies are also recognized in this article.

The year 2020 roughly corresponds with the 40th anniversary of the rise of political Islam on the world stage. This topic has generated controversy about its impact on Muslims societies and international affairs more broadly, including how governments should respond to this socio-political phenomenon. This article has modest aims. It seeks to reflect on the broad theme of political Islam four decades after it first captured global headlines by critically examining two separate but interrelated controversies. The first theme is political Islam's acquisition of state power. Specifically, how have the various experiments of Islamism in power effected the popularity, prestige, and future trajectory of political Islam? Secondly, the theme of political Islam and violence is examined. In this section, I interrogate the claim that mainstream political Islam acts as a "gateway drug" to radical extremism in the form of Al Qaeda or ISIS. This thesis gained popularity in recent years, yet its validity is open to question and should be subjected to further scrutiny and analysis. I examine these questions in this article.

The fundamental problem with this book is its deep Orientalist bias. To appreciate this point, imagine a book discussing African Americans and the rule of law. The key question this hypothetical book would seek to answer is whether African American culture is inhospitable to respecting the rule of law. Two schools of thought, the author suggests, should be studied. Black skeptics argue that a disdain for rule of law and an appetite for gang activity are hard-wired into African American culture with roots that go back to ancient African warrior religions. Black pluralists, by contrast, are more optimistic. They argue that under the right social conditions, African Americans can draw upon their cultural resources to be good citizens, respect the rule of law, and reject violence. Both schools of thought, the author emphatically asserts, are wrong yet they simultaneously contribute to understanding this subject. Black skeptics keep the debate honest,...

This study aimed to identify metallo-β-lactamases (MBLs) and AmpC β-lactamases-producing Escherichia coli isolates obtained from hemodialysis (HD) patients with urinary tract infections (UTI). A total of 257 HD patients with UTI were included in this study, from which 47 E. coli isolates were collected. Antibiotic susceptibility was tested by disc diffusion method. MBLs and AmpC production were phenotypically detected by imipenem-ethylenediaminetetracetate and cefoxitin/boronic acid assays, respectively. The presence of MBLs and AmpC genes was examined by polymerase chain reaction (PCR). Fosfomycin and ampicillin were the most and the least effective antibiotics against E. coli isolates, respectively. Moreover, 61.7% (29/47) of E. coli isolates were multidrug-resistant with seven different antibiotypes. Antibiotype V (AMP–CIP–IMP–MEM–CPD–CRO–CTX–GEN–LEV–SXT–TOB) was the most prevalent profile. Besides, 24 (51.1%) isolates were simultaneously resistant to imipenem and meropenem. Phenotypic assay showed MBL production in 16 (66.7%) of the 24 carbapenem-resistant E. coli isolates. The distribution of MBL genes in carbapenem-resistant E. coli was as follows: blaIMP 18 (72%), blaVIM 7 (28%), and blaNDM 1 (4%). AmpC was detected in 61.7% (29/47) of the isolates using the phenotypic method. The presence of AmpC genes was confirmed by PCR in only 26 of 29 (86.7%) AmpC producers. The frequencies of blaDHA-1, blaACC, and blaCMY-2 were 6 (20.7%), 11 (37.9%), and 21 (72.4%), respectively. The emergence of MBL and AmpC coproducing E. coli isolates calls for an urgent surveillance program for timely diagnosis and screening of these genes in our healthcare systems.

This chapter focuses on the problem of misunderstanding religious politics in the Arab-Islamic world. The goal is to advance an objective historical and comparative framework for interpreting this subject. Two key themes that have been central to John Esposito’s scholarship are examined: the secular bias in modernization theory and the need for a historical and contextual understanding of the many faces of political Islam. To advance this argument, Michael Walzer’s The Paradox of Liberation: Secular Revolutions and Religious Counterrevolutions will be utilized, focusing on his discussion of Algeria and political Islam. It is argued that Walzer offers a typical liberal reading of this topic that upon examination is ideologically biased and analytically distorting. Ironically, his earlier writings on religion and politics provide a more useful interpretive framework for understanding the rise of religious politics in our contemporary world.