A review of the zone broadening contributions in free-flow electrophoresis.

The broadening of analyte streams, as they migrate through a free-flow electrophoresis (FFE) channel, often limits the resolving power of FFE separations. Under laminar flow conditions, such zonal spreading occurs due to analyte diffusion perpendicular to the direction of streamflow and variations in the lateral distance electrokinetically migrated by the analyte molecules. Although some of the factors that give rise to these contributions are inherent to the FFE method, others originate from non-idealities in the system, such as Joule heating, pressure-driven crossflows, and a difference between the electrical conductivities of the sample stream and background electrolyte. The injection process can further increase the stream width in FFE separations but normally influencing all analyte zones to an equal extent. Recently, several experimental and theoretical works have been reported that thoroughly investigate the various contributions to stream variance in an FFE device for better understanding, and potentially minimizing their magnitudes. In this review article, we carefully examine the findings from these studies and discuss areas in which more work is needed to advance our comprehension of the zone broadening contributions in FFE assays.

TRPM2-mediated Ca2+ signaling as a potential therapeutic target in cancer treatment: an updated review of its role in survival and proliferation of cancer cells.

The transient receptor potential melastatin subfamily member 2 (TRPM2), a thermo and reactive oxygen species (ROS) sensitive Ca2+-permeable cation channel has a vital role in surviving the cell as well as defending the adaptability of various cell groups during and after oxidative stress. It shows higher expression in several cancers involving breast, pancreatic, prostate, melanoma, leukemia, and neuroblastoma, indicating it raises the survivability of cancerous cells. In various cancers including gastric cancers, and neuroblastoma, TRPM2 is known to conserve viability, and several underlying mechanisms of action have been proposed. Transcription factors are thought to activate TRPM2 channels, which is essential for cell proliferation and survival. In normal physiological conditions with an optimal expression of TRPM2, mitochondrial ROS is produced in optimal amounts while regulation of antioxidant expression is carried on. Depletion of TRPM2 overexpression or activity has been shown to improve ischemia-reperfusion injury in organ levels, reduce tumor growth and/or viability of various malignant cancers like breast, gastric, pancreatic, prostate, head and neck cancers, melanoma, neuroblastoma, T-cell and acute myelogenous leukemia. This updated and comprehensive review also analyzes the mechanisms by which TRPM2-mediated Ca2+ signaling can regulate the growth and survival of different types of cancer cells. Based on the discussion of the available data, it can be concluded that TRPM2 may be a unique therapeutic target in the treatment of several types of cancer. Video Abstract.

Recent advances and limitations of mTOR inhibitors in the treatment of cancer.

The PI3K-Akt-mechanistic (formerly mammalian) target of the rapamycin (mTOR) signaling pathway is important in a variety of biological activities, including cellular proliferation, survival, metabolism, autophagy, and immunity. Abnormal PI3K-Akt-mTOR signalling activation can promote transformation by creating a cellular environment conducive to it. Deregulation of such a system in terms of genetic mutations and amplification has been related to several human cancers. Consequently, mTOR has been recognized as a key target for the treatment of cancer, especially for treating cancers with elevated mTOR signaling due to genetic or metabolic disorders. In vitro and in vivo, rapamycin which is an immunosuppressant agent actively suppresses the activity of mTOR and reduces cancer cell growth. As a result, various sirolimus-derived compounds have now been established as therapies for cancer, and now these medications are being investigated in clinical studies. In this updated review, we discuss the usage of sirolimus-derived compounds and other drugs in several preclinical or clinical studies as well as explain some of the challenges involved in targeting mTOR for treating various human cancers.

Targeting Ras-ERK cascade by bioactive natural products for potential treatment of cancer: an updated overview.

MAPK (mitogen-activated protein kinase) or ERK (extracellular-signal-regulated kinase) pathway is an important link in the transition from extracellular signals to intracellular responses. Because of genetic and epigenetic changes, signaling cascades are altered in a variety of diseases, including cancer. Extant studies on the homeostatic and pathologic behavior of MAPK signaling have been conducted; however, much remains to be explored in preclinical and clinical research in terms of regulation and action models. MAPK has implications for cancer therapy response, more specifically in response to experimental MAPK suppression, compensatory mechanisms are activated. The current study investigates MAPK as a very complex cell signaling pathway that plays roles in cancer treatment response, cellular normal conduit maintenance, and compensatory pathway activation. Most MAPK inhibitors, unfortunately, cause resistance by activating compensatory feedback loops in tumor cells and tumor microenvironment components. As a result, innovative combinatorial treatments for cancer management must be applied to limit the likelihood of alternate pathway initiation as a possibility for generating novel therapeutics based on incorporation in translational research. We summarize current knowledge about the implications of ERK (MAPK) in cancer, as well as bioactive products from plants, microbial organisms or marine organisms, as well as the correlation with their chemical structures, which modulate this pathway for the treatment of different types of cancer.

Involvement of Resveratrol against Brain Cancer: A Combination Strategy with a Pharmaceutical Approach.

A brain tumor (BT) is a condition in which there is growth or uncontrolled development of the brain cells, which usually goes unrecognized or is diagnosed at the later stages. Since the mechanism behind BT is not clear, and the various physiological conditions are difficult to diagnose, the success rate of BT is not very high. This is the central issue faced during drug development and clinical trials with almost all types of neurodegenerative disorders. In the first part of this review, we focus on the concept of brain tumors, their barriers, and the types of delivery possible to target the brain cells. Although various treatment methods are available, they all have side effects or toxic effects. Hence, in the second part, a correlation was made between the use of resveratrol, a potent antioxidant, and its advantages for brain diseases. The relationship between brain disease and the blood-brain barrier, multi-drug resistance, and the use of nanomedicine for treating brain disorders is also mentioned. In short, a hypothetical concept is given with a background investigation into the use of combination therapy with resveratrol as an active ingredient, the possible drug delivery, and its formulation-based approach.

Monkeypox has devastated the world; should we prepare for the outbreak of a new pandemic?

The monkeypox virus, which belongs to the orthopoxy virus family, causes fever, lethargy, headache, lymphadenopathy, myalgia, and rash, as well as various complications such as superimposed infections, sepsis, keratitis, encephalitis, and bronchopneumonia. Following replication at the site of injection, the virus often enters by the oropharynx, nasopharynx, or intradermal pathway, spreading to lymph nodes before viremia, promoting viral dissemination to other organ systems. Monkeypox cases have recently been brought to WHO's notice from 12 presently non-endemic member nations spread over three WHO regions, with 92 laboratory-confirmed cases and 28 cases of suspicion as of May 21, 2022. Monkeypox is presently endemic in the Central African Republic, the Democratic Republic of the Congo, Benin, Cameroon, Gabon, Sierra Leone, and South Sudan. Monkeypox cases have been detected all across the world, posing a challenge to healthcare infrastructure that is still recovering from the COVID-19 outbreak. Close monitoring and exact data collecting, the implementation of successful programs across the world, and public support of preventative measures are some of the strategies being used to cope with the increasing incidence of monkeypox.

A Prospective Viewpoint on Neurological Diseases and Their Biomarkers.

Neurodegenerative diseases (NDDs) are disorders that affect both the central and peripheral nervous systems. To name a few causes, NDDs can be caused by ischemia, oxidative and endoplasmic reticulum (ER) cell stress, inflammation, abnormal protein deposition in neural tissue, autoimmune-mediated neuron loss, and viral or prion infections. These conditions include Alzheimer's disease (AD), Lewy body dementia (LBD), and Parkinson's disease (PD). The formation of ß-sheet-rich aggregates of intra- or extracellular proteins in the CNS hallmarks all neurodegenerative proteinopathies. In systemic lupus erythematosus (SLE), numerous organs, including the central nervous system (CNS), are affected. However, the inflammatory process is linked to several neurodegenerative pathways that are linked to depression because of NDDs. Pro-inflammatory signals activated by aging may increase vulnerability to neuropsychiatric disorders. Viruses may increase macrophages and CCR5+ T cells within the CNS during dementia formation and progression. Unlike medical symptoms, which are just signs of a patient's health as expressed and perceived, biomarkers are reproducible and quantitative. Therefore, this current review will highlight and summarize the neurological disorders and their biomarkers.

Vaccine dilemma for children at risk: Recently approved malaria vaccine versus ongoing COVID-19 vaccination campaign.

Recently, the World Health Organization (WHO) approved RTS, S/AS01 (RTS, S) as the world's first malaria vaccine for partial malaria protection in young children at risk. While this immunization drive begins during the unprecedented pandemic of the SARS-CoV-2 Virus, the WHO has also approved 7 Vaccines in 2021 for the vaccination of children at risk. This article explores the quandary that would occur to the officials in charge of carrying out large vaccination campaigns against these two deadly infectious illnesses in several regions including the continent of Africa. The article also outlines the priorities for resolving this dilemma, offers evidence-based solutions, and provides a summary of recent significant events and their consequences. While providing the latest data, a discussion on the causation of the dilemma with clear recommendations for possible solutions has been explored as well.

Multidrug Resistance in Cancer Cells: Focus on a Possible Strategy Plan to Address Colon Carcinoma Cells.

Even though various treatment methods are available for cancer, the death curve is not reducing. The diagnosis of cancer at the fourth stage and drug resistance are the leading reasons for treatment failure and lower survival rates. In this review article, we summarize the possible pitfalls during cancer treatment in general, which mainly include multidrug resistance, and propose a hypothesis for colorectal cancer specifically. We also evaluate multidrug resistance in cancer in general and colorectal cancer in particular and hypothesize a concept based on combination therapy with 5-fluorouracil, curcumin, and lipids for the possible management of colorectal cancer. In addition, a hypothetical approach, combining a synthetic agent and a natural chemotherapeutic agent, to treating colorectal cancer is also discussed. This hypothesis could improve the management of colorectal cancer.

Multidrug Resistance of Cancer Cells and the Vital Role of P-Glycoprotein.

P-glycoprotein (P-gp) is a major factor in the multidrug resistance phenotype in cancer cells. P-gp is a protein that regulates the ATP-dependent efflux of a wide range of anticancer medicines and confers resistance. Due to its wide specificity, several attempts have been made to block the action of P-gp to restore the efficacy of anticancer drugs. The major goal has been to create molecules that either compete with anticancer medicines for transport or function as a direct P-gp inhibitor. Despite significant in vitro success, there are presently no drugs available in the clinic that can "block" P-gp-mediated resistance. Toxicity, unfavourable pharmacological interactions, and a variety of pharmacokinetic difficulties might all be the reason for the failure. On the other hand, P-gp has a significant effect in the body. It protects the vital organs from the entry of foreign bodies and other toxic chemicals. Hence, the inhibitors of P-gp should not hinder its action in the normal cells. To develop an effective inhibitor of P-gp, thorough background knowledge is needed in this field. The main aim of this review article was to set forth the merits and demerits of the action of P-gp on cancer cells as well as on normal cells. The influence of P-gp on cancer drug delivery and the contribution of P-gp to activating drug resistance were also mentioned.

An Overview of Antimicrobial Stewardship Optimization: The Use of Antibiotics in Humans and Animals to Prevent Resistance.

Antimicrobials are a type of agent widely used to prevent various microbial infections in humans and animals. Antimicrobial resistance is a major cause of clinical antimicrobial therapy failure, and it has become a major public health concern around the world. Increasing the development of multiple antimicrobials has become available for humans and animals with no appropriate guidance. As a result, inappropriate use of antimicrobials has significantly produced antimicrobial resistance. However, an increasing number of infections such as sepsis are untreatable due to this antimicrobial resistance. In either case, life-saving drugs are rendered ineffective in most cases. The actual causes of antimicrobial resistance are complex and versatile. A lack of adequate health services, unoptimized use of antimicrobials in humans and animals, poor water and sanitation systems, wide gaps in access and research and development in healthcare technologies, and environmental pollution have vital impacts on antimicrobial resistance. This current review will highlight the natural history and basics of the development of antimicrobials, the relationship between antimicrobial use in humans and antimicrobial use in animals, the simplistic pathways, and mechanisms of antimicrobial resistance, and how to control the spread of this resistance.

Bioactive Based Nanocarriers for the Treatment of Viral Infections and SARS-CoV-2.

Since ancient times, plants have been used for their medicinal properties. They provide us with many phytomolecules, which serve a synergistic function for human well-being. Along with anti-microbial, plants also possess anti-viral activities. In Western nations, about 50% of medicines were extracted from plants or their constituents. The spread and pandemic of viral diseases are becoming a major threat to public health and a burden on the financial prosperity of communities worldwide. In recent years, SARS-CoV-2 has made a dramatic lifestyle change. This has promoted scientists not to use synthetic anti-virals, such as protease inhibitors, nucleic acid analogs, and other anti-virals, but to study less toxic anti-viral phytomolecules. An emerging approach includes searching for eco-friendly therapeutic molecules to develop phytopharmaceuticals. This article briefly discusses numerous bioactive molecules that possess anti-viral properties, their mode of action, and possible applications in treating viral diseases, with a special focus on coronavirus and various nano-formulations used as a carrier for the delivery of phytoconstituents for improved bioavailability.

Recent Advancements in Microneedle Technology for Multifaceted Biomedical Applications.

Microneedle (MNs) technology is a recent advancement in biomedical science across the globe. The current limitations of drug delivery, like poor absorption, low bioavailability, inadequate skin permeation, and poor biodistribution, can be overcome by MN-based drug delivery. Nanotechnology made significant changes in fabrication techniques for microneedles (MNs) and design shifted from conventional to novel, using various types of natural and synthetic materials and their combinations. Nowadays, MNs technology has gained popularity worldwide in biomedical research and drug delivery technology due to its multifaceted and broad-spectrum applications. This review broadly discusses MN's types, fabrication methods, composition, characterization, applications, recent advancements, and global intellectual scenarios.