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RNAi-Based Therapeutics and Novel RNA Bioengineering Technologies.

RNA interference (RNAi) provides researchers with a versatile means to modulate target gene expression. The major forms of RNAi molecules, genome-derived microRNAs (miRNAs) and exogenous small interfering RNAs (siRNAs), converge into RNA-induced silencing complexes to achieve posttranscriptional gene regulation. RNAi has proven to be an adaptable and powerful therapeutic strategy where advancements in chemistry and pharmaceutics continue to bring RNAi-based drugs into the clinic. With four siRNA medications already approved by the US Food and Drug Administration (FDA), several RNAi-based thera

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… By contrast, the genes of intragenic-derived miRNA are located within exons or introns of protein-coding genes, are coexpressed with their host gene, and are transcribed by RNA polymerase II ( Ha and Kim, 2014 ; Valinezhad Orang et al., 2014 ). … (A) Intragenic or intergenic miRNA genes are transcribed by RNA polymerases II or III into primary miRNA (pri-miRNA; >1,000 nucleotides) transcripts in canonical pathway (black lines). …

SARS-CoV-2 drug resistance and therapeutic approaches.

In light of the transition of COVID-19 from a pandemic to an endemic phase, there is still a dire need to address challenges associated with drug resistance, particularly among immunocompromised and high-risk populations. This review explores the current state of research on SARS-CoV-2 drug resistance and underscores the ongoing need for effective therapeutic strategies. It critically evaluates existing knowledge on resistance mechanisms and therapeutic options, aiming to consolidate information and highlight areas for future research. By examining the complex interactions between the virus an

Modulating epigenetic modifications for cancer therapy (Review).

Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non‑coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resist

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… A capped and polyadenylated RNA with a stem-loop structure is cleaved by Drosha to form genetically coded precursor miRNAs (pre-miRNAs) ( 140 ). miRNA genes are transcribed in the cell nucleus by RNA polymerase II giving rise to primary miRNAs (pri-miRNA) ( 141 ). … Precursor piRNAs (pre-piRNAs) are transcribed by RNA polymerase II. Once the newly transcribed RNA leaves the nucleus, pre-piRNAs interact with the germline-specific subclade or argonaute proteins known as PIWI proteins ( 148 ). …

MYC inhibitors in multiple myeloma.

The importance of MYC function in cancer was discovered in the late 1970s when the sequence of the avian retrovirus that causes myelocytic leukemia was identified. Since then, over 40 years of unceasing research have highlighted the significance of this protein in malignant transformation, especially in hematologic diseases. Indeed, some of the earliest connections among the higher expression of proto-oncogenes (such as MYC), genetic rearrangements and their relation to cancer development were made in Burkitt lymphoma, chronic myeloid leukemia and mouse plasmacytomas. Multiple myeloma (MM), in

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… polymerase II | Preclinical testing | Lim et al . [ 69 ] INCB054329 | JAK inhibitors † | Reduced expression of IL6R and STAT3 signaling. … They demonstrated a blockage in proliferation and enhanced apoptosis by decreasing the phosphorylation of RNA Polymerase II, reduction of MCL-1 and MYC proteins and MYC downregulation, resulting in a very significant tumor burden reduction. …

Targeting super enhancers for liver disease: a review.

BackgroundSuper enhancers (SEs) refer to the ultralong regions of a gene accompanied by multiple transcription factors and cofactors and strongly drive the expression of cell-type-related genes. Recent studies have demonstrated that SEs play crucial roles in regulating gene expression related to cell cycle progression and transcription. Aberrant activation of SEs is closely related to the occurrence and development of liver disease. Liver disease, especially liver failure and hepatocellular carcinoma (HCC), constitutes a major class of diseases that seriously endanger human health. Currently,

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… To interact with RNA polymerase II (RNAP II), P-TEFb must be recruited to transcriptional units ( Marshall et al., 1996 ; Marshall & Price, 1995 ; Peterlin & Price, 2006 ). … Control of RNA polymerase II elongation potential by a novel carboxyl-terminal domain kinase. The Journal of Biological Chemistry. 1996;271(43):27176–27183. doi: 10.1074/jbc.271.43.27176. Marshall & Price (1995) Marshall NF, Price DH. …

Upregulation of long non-coding RNA myocardial infarction-associated transcription is correlated with coronary artery stenosis and elevated inflammation in patients with coronary atherosclerotic heart disease.

Coronary atherosclerotic heart disease (CAD) is a chronic disease caused by multiple risk factors. Aberrant expression of long non-coding RNAs (lncRNAs) has been regarded as an independent risk factor of CAD. This study evaluated lncRNA myocardial infarction-associated transcription (MIAT) expression in CAD patients and its clinical significance. Totally, 155 CAD patients and 76 non-CAD controls were enrolled. MIAT expression was detected using reverse transcription quantitative polymerase chain reaction. The clinical diagnostic significance of MIAT was evaluated by plotting the receiver opera

Knockdown of lncRNA AL928768.3 inhibits multiple myeloma cell proliferation by inducing cell cycle arrest in G0/G1 phase.

BackgroundMultiple myeloma (MM) is a B-lymphocyte-derived malignancy. It ranks as the second most common hematological malignancy, with relatively high morbidity and mortality. However, the molecular mechanisms of MM occurrence and development remain elusive. This study found that long non-coding RNA AL928768.3 (lncRNA AL) was abnormally expressed in MM samples. However, the effect and molecular mechanism of lncRNA AL on the occurrence and development of MM remains unclear.MethodsBone marrow fluids of MM patients (n=54) and volunteers (n=13) were collected and CD138+ cells were isolated. The e

Litigations for HIV Related Complications

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Drug Combinations as a First Line of Defense against Coronaviruses and Other Emerging Viruses.

The world was unprepared for coronavirus disease 2019 (COVID-19) and remains ill-equipped for future pandemics. While unprecedented strides have been made developing vaccines and treatments for COVID-19, there remains a need for highly effective and widely available regimens for ambulatory use for novel coronaviruses and other viral pathogens. We posit that a priority is to develop pan-family drug cocktails to enhance potency, limit toxicity, and avoid drug resistance. We urge cocktail development for all viruses with pandemic potential both in the short term (<1 to 2 years) and longer term wi

Viruses

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Pharmacological treatments of COVID-19.

The viral infection due to the new coronavirus or coronavirus disease 2019 (COVID-19), which was reported for the first time in December 2019, was named by the World Health Organization (WHO) as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2), because of the very similar genome and also its related symptoms to SARS-CoV1. The ongoing COVID-19 pandemic with significant mortality, morbidity, and socioeconomic impact is considered by the WHO as a global public health emergency. Since there is no specific treatment available for SARS-CoV2 infection, and or COVID-19, several clinical and

Current Status of COVID-19 Therapies and Drug Repositioning Applications.

The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in dru

Acute Hepatitis C After Penile Stem Cell Injection.

Hepatitis C is a viral infection that is transmitted via blood or other bodily fluids and usually manifests as a chronic infection. We present a unique case of acute hepatitis C from a penile stem cell injection. Although previous cases have reported the reactivation of chronic hepatitis C after hematopoietic stem cell transplantation, it is uncommon for hepatitis C to present acutely, especially in an immunocompetent patient. To our knowledge, this is the first case of acute hepatitis C after a penile stem cell injection.

Potential drug development and therapeutic approaches for clinical intervention in COVID-19.

While the vaccination is now available to many countries and will slowly dissipate to others, effective therapeutics for COVID-19 is still illusive. The SARS-CoV-2 pandemic has posed an unprecedented challenge to researchers, scientists, and clinicians and affected the wellbeing of millions of people worldwide. Since the beginning of the pandemic, a multitude of existing anti-viral, antibiotic, antimalarial, and anticancer drugs have been tested, and some have shown potency in the treatment and management of COVID-19, albeit others failed to leave any positive impact and a few also became cont

The Role of DNA Repair in Genomic Instability of Multiple Myeloma.

Multiple Myeloma (MM) is a B cell malignancy marked by genomic instability that arises both through pathogenesis and during disease progression. Despite recent advances in therapy, MM remains incurable. Recently, it has been reported that DNA repair can influence genomic changes and drug resistance in MM. The dysregulation of DNA repair function may provide an alternative explanation for genomic instability observed in MM cells and in cells derived from MM patients. This review provides an overview of DNA repair pathways with a special focus on their involvement in MM and discusses the role th

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… In contrast, TC-NER is activated when RNA polymerase II (RNA Pol II) is stalled during transcription in the template strand. …

A Possible Role of Remdesivir and Plasma Therapy in the Selective Sweep and Emergence of New SARS-CoV-2 Variants.

Since summer 2020, SARS-CoV-2 strains at the origin of the COVID-19 pandemic have suddenly been replaced by new SARS-CoV-2 variants, some of which are highly transmissible and spread at a high rate. These variants include the Marseille-4 lineage (Nextclade 20A.EU2) in Europe, the 20I/501Y.V1 variant first detected in the UK, the 20H/501Y.V2 variant first detected in South Africa, and the 20J/501Y.V3 variant first detected in Brazil. These variants are characterized by multiple mutations in the viral spike protein that is targeted by neutralizing antibodies elicited in response to infection or

Liquid biopsy and PCR-free ultrasensitive detection systems in oncology (Review).

In oncology, liquid biopsy is used in the detection of next-generation analytes, such as tumor cells, cell-free nucleic acids and exosomes in peripheral blood and other body fluids from cancer patients. It is considered one of the most advanced non-invasive diagnostic systems to enable clinically relevant actions and implement precision medicine. Medical actions include, but are not limited to, early diagnosis, staging, prognosis, anticipation (lead time) and the prediction of therapy responses, as well as follow-up. Historically, the applications of liquid biopsy in cancer have focused on cir

Innovative laboratory techniques shaping cancer diagnosis and treatment in developing countries.

Cancer is a major global health challenge, with approximately 19.3 million new cases and 10 million deaths estimated by 2020. Laboratory advancements in cancer detection have transformed diagnostic capabilities, particularly through the use of biomarkers that play crucial roles in risk assessment, therapy selection, and disease monitoring. Tumor histology, single-cell technology, flow cytometry, molecular imaging, liquid biopsy, immunoassays, and molecular diagnostics have emerged as pivotal tools for cancer detection. The integration of artificial intelligence, particularly deep learning and

Systemic Sclerosis Association with Malignancy.

The association of systemic sclerosis (SSc) and cancer is well known from several decades suggesting common genetic and environmental risk factors involved in the development of both diseases. Immunosuppressive drugs widely used in SSc may increase the risk of cancer occurrence and different SSc clinical and serological features identify patients at major risk to develop malignancy. In this context, among serological features, presence of anti-RNA polymerase III and anti-topoisomerase I autoantibodies seems to increase cancer frequency in SSc patients (particularly lung and breast cancers). Lu…

The convergent evolution of influenza A virus: Implications, therapeutic strategies and what we need to know.

Influenza virus infection, more commonly known as the 'cold flu', is an etiological agent that gives rise to recurrent annual flu and many pandemics. Dated back to the 1918- Spanish Flu, the influenza infection has caused the loss of many human lives and significantly impacted the economy and daily lives. Influenza virus can be classified into four different genera: influenza A-D, with the former two, influenza A and B, relevant to humans. The capacity of antigenic drift and shift in Influenza A has given rise to many novel variants, rendering vaccines and antiviral therapies useless. In light

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… The miRNA is transcribed by RNA polymerase II, giving a Pri-miRNA containing a 5′- cap structure and a polyA-tail. …