Globally, cancer is amongst the most deadly diseases due to the low efficiency of the conventional and obsolete chemotherapeutic methodologies and their many downsides. The poor aqueous solubility of most anticancer medications and their low biocompatibility make them ineligible candidates for the design of delivery systems. A significant drawback associated with chemotherapy is that there are no advanced solutions to multidrug resistance, which poses a major obstacle in cancer management. Since RNA interference (RNAi) can repress the expression of genes, it is viewed as a novel tool for advanced drug delivery. this is being explored as a promising drug targeting strategy for the treatment of multiple diseases, including cancer. However, there are many obstructions that hinder the clinical uses of siRNA drugs due to their low permeation into cells, off-target impacts, and possible unwanted immune responses under physiological circumstances. Thus, in this article, we review the design measures for siRNA conveyance frameworks and potential siRNA and miRNA drug delivery systems for malignant growth treatment, including the use of liposomes, dendrimers, and micelle-based nanovectors and functional polymer–drug delivery systems. This article sums up the advancements and challenges in the use of nanocarriers for siRNA delivery and remarkably centers around the most critical modification strategies for nanocarriers to build multifunctional siRNA and miRNA delivery vectors. In short, we hope this review will throw light on the dark areas of RNA interference, which will further open novel research arenas in the development of RNAi drugs for cancer.
Antimicrobial peptides (AMPs) are natural compounds that are primarily used in the development of new therapeutic components for a variety of illnesses, such as infectious diseases, parasitic illnesses, cancer, etc. Due to the rising occurrence of drug resistance, AMPs are used the same as antibiotics. Since the discovery of the first AMP, numerous studies have been conducted to determine the importance of amino acid residues showing antimicrobial activity and to develop and characterize potential AMPs. Since wet-lab experimental identification requires a lot of effort and cost, in silico studies are widely used to identify novel AMP candidates. In silico studies aid in the identification and modeling of AMPs. However, wet-lab studies using assays are assisting in characterizing the newly identified AMPs and their therapeutic potential. Thus, a number of researches helped to uncover the diversity of AMPs as well as the different classes within them. In this book chapter, we cover a wide range of AMP classifications, the mechanism of action of AMPs, various AMP-based drugs identified so far for treating parasitic diseases. Also, we illustrate how the approach of AMPs has helped in finding out remedies for Malaria. Additionally, we explain computational methods and resources for better research in the field of AMPs studies.
In the original publication [...].
The advancement of multidrug-resistant bacterial strains and their adverse effects is one of the most significant global health issues. The perovskite nanomaterial with combined antioxidant and antibacterial activities in one molecule has the potential for improved therapeutic solutions. In this work, Yttrium-doped Lanthanum Titanate (LaTi 1 − x Y x O 3 , where x = 0, 0.05, and 0.1) was synthesized using auto combustion technique. Excellent crystalline structure with a tetragonal system is revealed by X-ray diffraction analysis (XRD). UV–Visible diffuse reflectance spectroscopy (UV–Vis DRS), Fourier transform infrared (FTIR), and photoluminescence (PL) were used to study its optical characteristics. The field emission scanning electron microscope (FE-SEM) shows rod-like pellet-shaped Yttrium-doped nanostructures, and the elements present were confirmed with the Energy Dispersive X-Ray Analysis (EDAX). Various concentrations of the synthesized materials were tested for antibacterial activity against Gram-positive ( Staphylococcus aureus 902) and Gram-negative ( E. coli 443) strains using the agar-well diffusion method with gentamicin antibiotic as a positive control. High antibacterial activity of 87.1% and 83.3% was shown by 10% Yttrium-doped LaTiO 3 (LY(0.1)TO) at 500 mg/mL against both positive and negative stains, respectively. Moreover, the antioxidant properties of synthesized materials were assessed with IC50 values of 352.33 µg/mL, 458.055 µg/mL, and 440.163 µg/mL for samples LaTi 1 − x Y x O 3 , where x = 0, 0.05, and 0.1 respectively. The antibacterial and antioxidant capabilities of the proposed samples illustrate their applicability in various biomedical applications.
Breast and gynecologic cancers are significant global threats to women's health and those living with the disease require lifelong physical, financial, and social support from their families, healthcare providers, and society as a whole. Cancer vaccines offer a promising means of inducing long-lasting immune response against the disease. Among various types of cancer vaccines available, peptide vaccines offer an effective strategy to elicit specific anti-tumor immune responses. Peptide vaccines have been developed based on tumor associated antigens (TAAs) and tumor specific neoantigens which can also be of viral origin. Molecular alterations in HER2 and non-HER2 genes are established to be involved in the pathogenesis of female-specific cancers and hence were exploited for the development of peptide vaccines against these diseases, most of which are in the latter stages of clinical trials. However, prophylactic vaccines for viral induced cancers, especially those against Human Papillomavirus (HPV) infection are well established. This review discusses therapeutic and prophylactic approaches for various types of female-specific cancers such as breast cancer and gynecologic cancers with special emphasis on peptide vaccines. We also present a pipeline for the design and evaluation of a multiepitope peptide vaccine that can be active against female-specific cancers.
Purpose The study explores the perspectives of college students on the pedagogical shift as well as frequent transitions between online and offline learning modes during the COVID-19 pandemic in Kerala, the most literate state in India. Design/methodology/approach A descriptive cross-sectional study was conducted among 1,366 college students in Kerala during December 2021. A pre-tested questionnaire was sent using Google Forms to students of arts and science colleges. The authors analyzed quantitative data using descriptive statistics and qualitative data using thematic content analysis. Findings The reported advantages of online learning were increased technical skill, flexibility in study time, effectiveness in bridging the gap of the missed academic period and provision of attending more educational webinars. Students expressed concerns of increased workload, difficulty in concentration due to family circumstances, academic incompetency, uncleared doubts and addiction to mobile phones and social media during the online classes. The main advantages reported for switching to an offline learning mode were enhanced social interaction, effective learning, better concentration and reduced stress. The reported challenges of offline classes were fear of getting the disease, concern of maintaining social distancing and difficulty in wearing masks during the classes. The shift in offline to online learning and vice versa was perceived as a difficult process for the students as it took a considerable time for them to adjust to the switching process of learning. Originality/value Students' concerns regarding transition between different learning modes provide important information to educators to better understand and support the needs of students during the pandemic situations.
Background: The risk of SARS-CoV-2 infection and severity with disease modifying therapies (DMTs) in multiple sclerosis (MS) remains unclear, with some studies demonstrating increased risks of infection with B-celldepleting (anti-CD20) therapies and severity, while others fail to observe an association. Most existing studies are limited by a reliance on 'numerator' data (i.e., COVID-19 cases) only. Objective: To assess the risks of COVID-19 by DMT, this study aimed to assess both 'numerator' (patients with SARS-CoV-2 infection) and 'denominator' data (all patients treated with DMTs of interest) to determine if any DMTs impart an increased risk of SARS-CoV-2 infection or disease severity.Methods: We systematically reviewed charts and queried patients during clinic encounters in the NYU MS Comprehensive Care Center (MSCCC) for evidence of COVID-19 in all patients who were on the most commonly used DMTs in our clinic (sphingosine-1-phosphate receptor (S1P) modulators (fingolimod/siponimod), rituximab, ocrelizumab, fumarates (dimethyl fumarate/diroximel fumarate), and natalizumab). COVID-19 status was determined by clinical symptoms (CDC case definition) and laboratory testing where available (SARS-CoV-2 PCR, SARS-CoV-2 IgG). Multivariable analyses were conducted to determine predictors of infection and severe disease (hospitalization or death) using SARS-CoV-2 infected individuals per DMT group and all individuals on a given DMT as denominator.Results: We identified 1,439 MS patients on DMTs of interest, of which 230 had lab-confirmed (n = 173; 75.2%) or suspected (n = 57; 24.8%) COVID-19. Infection was most frequent in those on rituximab (35/138; 25.4%), followed by fumarates (39/217; 18.0%), S1P modulators (43/250; 17.2%), natalizumab (36/245; 14.7%), and ocrelizumab (77/589; 13.1%). There were 14 hospitalizations and 2 deaths. No DMT was found to be significantly associated with increased risk of SARS-CoV-2 infection. Rituximab was a predictor of severe SARS-CoV-2 infection among patients with SARS-CoV-2 infection (OR 6.7; 95% CI 1.1-41.7) but did not reach statistical significance when the entire patient population on DMT was used (OR 2.8; 95% CI 0.6-12.2). No other DMT was associated with an increased risk of severe COVID-19.Conclusions: Analysis of COVID-19 risk among all patients on the commonly used DMTs did not demonstrate increased risk of infection with any DMT. Rituximab was associated with increased risk for severe disease.
RNA interference is a transformative approach and has great potential in the development of novel and more efficient cancer therapeutics. Immense prospects exist in the silencing of HER2 and its downstream genes which are overexpressed in many cancers, through exogenously delivered siRNA. However, there is still a long way to exploit the full potential and versatility of siRNA therapeutics due to the challenges associated with the stability and delivery of siRNA targeted to specific sites. Aptamers offer several advantages as a vehicle for siRNA delivery, over other carriers such as antibodies. In this review, we discuss the progress made in the development and applications of aptamer-siRNA chimeras in HER2 targeting and gene silencing. A schematic workflow is also provided which will provide ample insight for all those researchers who are new to this field. Also, we think that a mechanistic understanding of the HER2 signaling pathway is crucial in designing extensive investigations aimed at the silencing of a wider array of genes. This review is expected to stimulate more research on aptamer-siRNA chimeras targeted against HER2 which might arm us with potential effective therapeutic interventions for the management of cancer.
Pathogenic viruses with an RNA genome represent a challenge for global human health since they have the tremendous potential to develop into devastating pandemics/epidemics. The management of the recent COVID-19 pandemic was possible to a certain extent only because of the strong foundations laid by the research on previous viral outbreaks, especially Ebola Virus Disease (EVD). A clear understanding of the mechanisms of the host immune response generated upon viral infections is a prime requisite for the development of new therapeutic strategies. Hence, we present here a comparative study of alterations in immune response upon SARS-CoV-2 and Ebola virus infections that illustrate many common features. Vaccination and pregnancy are two important aspects that need to be studied from an immunological perspective. So, we summarize the outcomes and immune responses in vaccinated and pregnant individuals in the context of COVID-19 and EVD. Considering the significance of immunomodulatory approaches in combating both these diseases, we have also presented the state of the art of such therapeutics and prophylactics. Currently, several vaccines against these viruses have been approved or are under clinical trials in various parts of the world. Therefore, we also recapitulate the latest developments in these which would inspire researchers to look for possibilities of developing vaccines against many other RNA viruses. We hope that the similar aspects in COVID-19 and EVD open up new avenues for the development of pan-viral therapies.
Life science is the study of living organisms, including bacteria, plants, and animals. Given the importance of biology, chemistry, and bioinformatics, we anticipate that this chapter may contribute to a better understanding of the interdisciplinary connections in life science. Research in applied biological sciences has changed the paradigm of basic and applied research. Biology is the study of life and living organisms, whereas science is a dynamic subject that as a result of constant research, new fields are constantly emerging. Some fields come and go, whereas others develop into new, well-recognized entities. Chemistry is the study of composition of matter and its properties, how the substances merge or separate and also how substances interact with energy. Advances in biology and chemistry provide another means to understand the biological system using many interdisciplinary approaches. Bioinformatics is a multidisciplinary or rather transdisciplinary field that encourages the use of computer tools and methodologies for qualitative and quantitative analysis. There are many instances where two fields, biology and chemistry have intersection. In this chapter, we explain how current knowledge in biology, chemistry, and bioinformatics, as well as its various interdisciplinary domains are merged into life sciences and its applications in biological research.
To determine whether frequency and severity of COVID-19 differ by disease modifying therapy (DMTs) among patients with multiple sclerosis (MS) and other central nervous system immune-mediated disorders.
When a new infectious disease emerges as an epidemic or pandemic, strict and appropriate mitigation strategies are critical. Appropriate steps that facilitate defining of cases, carrying out accurate clinical diagnoses, and forming a powerful health surveillance that addresses public health policies and procedures are necessary. Tracking the number of COVID-19 cases over time and flattening the curve is another important element to establish research settings and identify therapeutic components to expedite and develop effective interventions. Addressing the various sections of the society in a philanthropic way is crucial to acquiring the public cooperation that is essential to controlling a disease like COVID-19. In this study, we discuss various strategies and measures adopted by Kerala, an Indian state, to combat the COVID-19 outbreak. Regular and timely updates by government public relations and health departments were used in many of the adopted strategies. The engagement of health information systems, together with the application of decentralized governance and community engagement, has contributed to effective population health management and surveillance of the pandemic.
Recent advances in peptide research revolutionized therapeutic discoveries for various infectious diseases. In view of the ongoing threat of the COVID-19 pandemic, there is an urgent need to develop potential therapeutic options. Intense and accomplishing research is being carried out to develop broad-spectrum vaccines and treatment options for corona viruses, due to the risk of recurrent infection by the existing strains or pandemic outbreaks by new mutant strains. Developing a novel medicine is costly and time consuming, which increases the value of repurposing existing therapies. Since, SARS-CoV-2 shares significant genomic homology with SARS-CoV, we have summarized various peptides identified against SARS-CoV using in silico and molecular studies and also the peptides effective against SARS-CoV-2. Dissecting the molecular mechanisms underlying viral infection could yield fundamental insights in the discovery of new antiviral agents, targeting viral proteins or host factors. We postulate that these peptides can serve as effective components for therapeutic options against SARS-CoV-2, supporting clinical scientists globally in selectively identifying and testing the therapeutic and prophylactic agents for COVID-19 treatment. In addition, we also summarized the latest updates on peptide therapeutics against SARS-CoV-2.
We report the case of a man who presented with anterograde memory deficit due to bilateral hippocampal lesions in the setting of cocaine and amyl nitrate use.
ABSTRACTBackgroundLittle is known regarding long-term outcomes of patients hospitalized with COVID-19.MethodsWe conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep.ResultsOf 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N=196 neurological patients and N=186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on ≥1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 2.03, 95%CI 1.22-3.40, P=0.01), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P=0.01) and were less likely to return to work than controls (41% versus 64%, P=0.04). Cognitive and Neuro-QOL metrics were similar between groups.ConclusionsAbnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.
Molecular mimicry is a general strategy used by pathogens to infect the host cells. The emergence of SARS-CoV-2 virus has resulted in more than 6,700,000 infections and 390,000 deaths worldwide. Coronavirus disease (COVID-19) is an infectious disease caused by this virus. In this project concept, we aim to focus on the peptide-protein interaction analysis using two important drug targets in SARS-CoV-2 such as spike (S) protein and nucleocapsid (N) protein. These proteins play an important role in the virus entry and encapsidation of the viral particles. Motifs or functional regions in these two proteins must be sharing sequence homology with human protein (ACE2) which may be involved in the binding mechanism. The results will show a set of motif regions which can disrupt the viral infection. Once we identify these sets of antigenic determinant regions, antibody binding activity studies can be performed by in vitro methods. Our results from this study may suggest the existence of antigenic mimicry between SARS-CoV-2 and host proteins. The hit peptide components will have therapeutic applications to be developed into a wide variety of medicinal formulations against SARS-CoV-2 such as vaccine, intranasal and inhalation formulations. Also, the choice of conserved regions will lead to development of cross protective therapeutics against wide range of coronaviruses.