Papers by Ashok Chakraborty
Cancer science & research, Dec 30, 2022
Macrophages (MΦs) are functionally plastic and can rapidly adopt different phenotypes based on th... more Macrophages (MΦs) are functionally plastic and can rapidly adopt different phenotypes based on the stimuli they received from their surroundings. For instance, (MΦs) can differentiate into pro-inflammatory M1-type secreting various pro-inflammatory cytokines, e.g., IL-6, IL-12 and TNF-α. This is an essential defensive mechanism against invading pathogens, but also contributes to tissue destruction. On the other hand, M2-type MΦs have immunosuppressive activity, produces high level of anti-inflammatory cytokine IL-10 and mediates tissue repair. Their unique plasticity and the balance in between different phenotypes maintain the immune homeostasis in the lung under healthy conditions. The role of these two forms of MΦs are also evident in cancer biology. While tissue resident MΦs those who are of M1 type are exerting the immune challenge to the tumor cells, the M2 type from the tumor microenvironment (TME) are supporting the growth and progression of cancer cells. Nanodevices are thought to be an ideal agent targeting macrophages owing to their intrinsic nanoscale property suitable for phagocytosis. The induction of MΦs polarization has been employed in various studies, where administration of IL-4 could reprogram the endogenous inflammatory macrophages (M1-type) to anti-inflammatory ones (M2-type), and accelerate resolution of inflammation and lung repair in a STAT6-dependent manner in both LPS and Pseudomonas aeruginosa bacterial pathogen-induced ALI (Acute Lung Injury) mouse models.
Archives of Medical Science, 2012
Introduction: To screen the risk factors associated with breast cancer among Chinese women in ord... more Introduction: To screen the risk factors associated with breast cancer among Chinese women in order to evaluate the individual risk of developing breast cancer among women in China. Material and methods: A case-control study on 416 breast cancer patients and 1156 matched controls was conducted in 14 hospitals in 8 provinces of China in 2008. Controls were age-and region-matched to the cases. Clinicians conducted in-person interviews with the subjects to collect information on demographics and suspected risk factors for breast cancer that are known worldwide. Conditional logistic regression was used to derive odds ratios (OR) and 95% confidence intervals (CI) for the associations between risk factors and breast cancer. Results: Compared with matched controls, women with breast cancer were significantly more likely to have higher body mass index (BMI,
MedPress Neurology and Neurosurgery, Mar 28, 2022
A Brief Notes on Gene Therapy, Cell Therapy and Cell-Based Gene Therapy for Alzheimer's Disease A... more A Brief Notes on Gene Therapy, Cell Therapy and Cell-Based Gene Therapy for Alzheimer's Disease Alzheimer's disease (AD) is known as an age-related neurodegenerative disease where progressive loss of memory associated with cognition defects has been noticed. Molecular analysis of AD revealed the formation of aggregated amyloid-β protein and hyper phosphorylated tau tangles at the synaptic circuit, which causes the loss of neuronal communication. At present no cure has been found for AD, but there are many new therapeutic approaches being attempted. For instance, the development of stem cell therapy is one approach for AD. In this review we highlight the merits and demerits of stem cell-based therapy, gene therapy for AD and proposed gene-modified cell therapy for AD treatment.
Medical journal of clinical trials & case studies, 2021
As of today seven coronaviruses were identified to infect humans, out of which only 4 of them bel... more As of today seven coronaviruses were identified to infect humans, out of which only 4 of them belongs to beta family of coronavirus, like HCoV-HKU1, SARS-CoV-2, MERS-CoV and SARS-CoV. SARS family viruses were known to cause severe respiratory disease in humans. SARS-CoV-2 has recently considered as a pandemic with over 100 M confirmed cases and over 1.5 M death worldwide. Vaccines and antibodies appeared as record pace. However, generation of variants has already been demonstrated as an escape of virus from a particular vaccine therapy. Therefore, a broad-spectrum anti-CoV therapies should be emphasized.
PDF file - 1.1MB, Figure S1. Single agent concentration-effect curves, related to Figure 1; Figur... more PDF file - 1.1MB, Figure S1. Single agent concentration-effect curves, related to Figure 1; Figure S2. Drug class and concentration choices for combinatorial drug screening, related to Figure 2; Figure S3, Mutant BRAF and mutant RAS selective drug pairs, related to Figure 3; Figure S4. Analysis of drug combinations by target class, related to Figure 4D; Figure S5. Sensitization of mutant BRAF lines with lapatinib and MK-2206, related to Figure 5; Figure S6. Immunoblot analyses of vemurafenib-resistant lines after drug treatments, related to Figure 5; Figure S7. Signaling and biological effects of simvastatin and flavopiridol in vitro and in vivo, related to Figure 6
Mechanism of Antiviral Activities of Nanoviricide's Platform Technology based Biopolymer (NV-CoV-2)
AIMS Public Health
NV-CoV-2 is a nanoviricide that is covalently bonded with polyethylene glycol (PEG) and alkyl pen... more NV-CoV-2 is a nanoviricide that is covalently bonded with polyethylene glycol (PEG) and alkyl pendants. This molecular design is used to attack many strains of coronaviruses in a broad-spectrum manner. The ligand works by competitive inhibition and binds to the same site on the S-protein of SARS-CoV that attaches to the cognate cellular receptor, ACE2. This prevents SARS-CoV from binding and infecting the cell. NV-CoV-2 is designed to bind to the free virion particles at multiple points encapsulate the virus and disable its ability to infect the cells. The multi-point binding interaction, like a nano-velcro-tape, may lead to lipid-lipid fusion of the alkyl chains in the nanoviricide micelle with the lipid envelope of the virus. The virus becomes dismantled to a capsid form before the host immune system becomes involved. This putative mechanism is orthogonal to many other anti-coronavirus agents in development. Thus, it maybe possible to produce a stronger antiviral effect when combi...
Depression and Parkinson's disease: a Chicken-Egg story
AIMS Neuroscience
Parkinson's disease (PD) is a neurodegenerative disease, however, besides the motor symptoms,... more Parkinson's disease (PD) is a neurodegenerative disease, however, besides the motor symptoms, such as rest tremor, hypokinesia, postural instability and rigidity, PD patients have also non-motor symptoms, namely neuropsychiatric disorders. Apart from the required motor symptoms, psychopathological symptoms are very common and include mood disorders, anxiety disorders, hallucinations, psychosis, cognitive deterioration and dementia. The underlying pathophysiological process in PD is mainly due to the loss of dopaminergic neural cells and thereby causes the shortage of nigrostriatal dopamine content in them. In addition, it may involve other neurotransmitter systems such as the noradrenergic, serotonergic, cholinergic and noradrenergic systems as well. Depression can result from any unhealthy conditions making the diagnosis a challenging task. The manifestation of depression associated with or without PD is inadequate. The co-occurrence of depression and PD often leads to the conc...
Journal of Medical – Clinical Research & Reviews
A recent clinical trial (Clinical Trial: NCT04315948) by Florence Ader et al., published on the p... more A recent clinical trial (Clinical Trial: NCT04315948) by Florence Ader et al., published on the preprint server medRxiv (Posted April 12, 2022), reported that RDV was not associated with clinical improvement at day 15 or day 29, nor with a reduction in mortality, nor with a reduction in SARS-CoV-2 RNA. In cell culture studies with SARS-CoV-2 infection in a variety of cell types, the antiviral effect of RDV was satisfactory. However, the authors of this clinical trial state that the efficacy of the drug and its toxicity in humans is over predicted. However, we came up with our own evaluation from our most relevant experimental results.
Neurology and Neuroscience
Amyotrophic lateral sclerosis (ALS) is a non-demyelinating neurodegenerative disease mostly found... more Amyotrophic lateral sclerosis (ALS) is a non-demyelinating neurodegenerative disease mostly found in adults between 40 to 60 years old. This disease is usually prevalent in males, however it’s irrespective to the different genders. ALS is progressive and within 2-5 years of diagnosis ulimately ends with death. The majority of ALS cases is sporadic (90%) and is recorded without any defined aetiology. The other 10-12% of cases is recognized from mutations in more than 20 genes. The genes reported to cause ALS are Superoxide Dismutase 1 (SOD1), TAR DNA Binding Protein (TDP), Fused in Sarcoma, (FUS), Chromosome 9 Open Reading Frame 72 (c9orf72) and Vesicle-Associated Membrane-ProteinAssociated Protein B (VAPB). Furthermore, abnormal lipid metabolism with higher LDL/HDL ratio was reported in ALS patients. The aetiology of ALS is shown in the schematic diagram below (Figure 1) Due to the multi-nature of ALS causative factors and symptoms, there is no specific therapy for ALS today. Howeve...
Frontiers in Nanotechnology
NV-CoV-2, a nanoviricide composed of covalently attached polyethylene glycol and alkyl pendants t... more NV-CoV-2, a nanoviricide composed of covalently attached polyethylene glycol and alkyl pendants that are designed to bind free virion particles of multiple strains of coronaviruses in a broad-spectrum manner at multiple points. The binding interaction is like a nano-velcro-tape and may cause a lipid–lipid fusion between nanoviricide micelle and the lipid envelope of the virus. A nanoviricide can encapsulate the virus and dismantle it without any involvement of the host immune system, ultimately disabling the infectibility of the host cells. Thus, it may be expected to count a stronger and synergistic antiviral effect by combining NV-CoV-2 with other anti-coronavirus regimens like remdesivir. Furthermore, some ligands similar to the SARS-CoV S-protein are designed by molecular modeling and attached to the nanoviricide at the same site as where the cognate cellular receptor, ACE2, binds. As a result, a competitive binding inhibition may occur. A nanoviricide can encapsulate other anti...
The effect of tryptophan on dopa-oxidation by melanosomal tyrosinase
International Journal of Biochemistry, 1993
1. Tryptophan has been shown to inhibit dopa-oxidation by melanosomal tyrosinase. 2. The inhibiti... more 1. Tryptophan has been shown to inhibit dopa-oxidation by melanosomal tyrosinase. 2. The inhibition is of mixed-type with Ki = 1.6 x 10(-3) M. 3. Tryptophan does not interact with the oxidation product of the dopa-oxidase reaction. 4. Neither oxygen nor hydroxyl radicals are involved in the inhibition found in presence of tryptophan. 5. Tryptophan, like dopa, also inhibits tyrosine hydroxylase and dopa-oxidase activity of melanosomal tyrosinase and its inhibitory mechanism differs from inhibition due to non-substrate type compounds like cysteine, ascorbic acid. 6. These experiments together with previous findings suggest that the status of tryptophan may be similar to that of dopa in relation to regulation of melanogenesis.
Journal of Neurology and Neurophysiology, 2020
Here we will review whether and how hNSCs could be modified to a better growing cells with increa... more Here we will review whether and how hNSCs could be modified to a better growing cells with increased survival length along with differentiation and Dopamine producing ability, using cell-cell interaction approach. A: Cell-Cell interaction is vastly studied in cancer biology. Cancer cells not only interact with themselves but also respond to tumor microenvironment (TME) containing growth factors, cytokines, and extracellular matrix proteins [14-16]. The interactions between normal and cancer cells can be either tumor-suppressive [17-22]. Cancer-associated fibroblasts can promote growth and invasion of the cancer cells [23]. Further, Cancer cells elongate blood vessels in TME by interaction with endothelial cells [24]. Overall, cell-cell communication in the Tumor Microenvironment (TME) is the biggest barrier to challenge the disease [25]. Cancer cells can modify the host cells to have tumor-supportive traits, and the modified host cells by interacting with cancer cells contribute to tumor progression. Therefore, understanding cell-cell interaction within TME can provide insight into cancer biology, and also in identifying new Neural cells being dopaminergic can be used for cell replacement therapy of Parkinson's Disease (PD). PD results when Dopamine release in the brain becomes less due to the death of neural cells. Therefore, replacement of neural cells in the brain if can be done from outside, is believed to restore the Dopamine level that can combat the PD-related symptoms. Neural stem cells (NSCs) is a better choice than many other cells that can also be thought for the same purposes (recently reviewed by Chakraborty and Diwan). Further, equipped with the systems in maintaining the controlled level of dopamine, these hNSC cells do not cause any future dopamine-associated problems, like dyskinesia, motor neuron defect in the individual. However, NSCs grow very slowly and senescence occur after few passages, therefore practically may not be feasible to collect many cells for the treatment of a number PD patients. Here we will discuss an option to modify the cells for its better growth and survival length as well as it's dopaminergic ability. Cell-Cell interaction are commonly known to modify the cells, and may be considered for the above purpose.
Journal of Experimental Neurology, 2020
Approximately 5.5 million people in the United States and 47 million people worldwide are current... more Approximately 5.5 million people in the United States and 47 million people worldwide are currently affected by AD [2,3]. It is expected that by 2050, nearly a million new cases per year may develop [4]. Symptoms: What are the symptoms of AD Memory loss is usually the first sign of AD which is different than normal memory problems. Unlike in other cases where one can forget something for the time being but can recollect later, AD person's loss of memory is irreversible. Followings are the symptoms associated with mild, moderate, and severe AD. Symptoms vary as the disease progresses (Figure 1). Mild AD: Usually, a person with mild AD avoids new and unfamiliar situations; has trouble learning and remembering new information, speaks more slowly than in the past; makes wrong decisions; may have mood swings and become depressed, grouchy, or restlessness [5].
Coronavirus management and control: Nutrition and alternative medicines
Nutrition and Health
Background: In late December 2019, the outbreak of COVID-19 caused by the coronavirus severe acut... more Background: In late December 2019, the outbreak of COVID-19 caused by the coronavirus severe acute respiratory syndrome-CoV-2, originated in Wuhan Province, the People’s Republic of China (PRC). The rapid and highly infectious virus quickly spread around the country and has become a global pandemic. Thousands of people have been infected, and have died. Scientists around the world are working on the vaccine; however, an effective cure is yet to be developed. Aims: Search to be made on some alternative antiviral components from the rich sources of traditional herbal medicine in India as well as in the PRC. Here we discuss them with references. Methods: The knowledge gained from the literature search of antiviral known herbal products or Ayurvedic medicines that used to be applied against any viral or bacterial infections in the past, may be considered for deployment against COVID-19, and may be rewarded. Results: Many medicinal compounds are extracted from plants and have led to drug...
Biomedical Research and Clinical Reviews
Chronic neuro-inflammation cause the neural cell death including dopaminergic cells and ultimate ... more Chronic neuro-inflammation cause the neural cell death including dopaminergic cells and ultimate results Parkinson’s disease (PD). In an MPTP-induced PD animal model an increased peripheral pro-inflammatory M1 macrophages (M1- MFs) were found. Polarization of this M1-type of MFs to anti-inflammatory M2-type revealed a potential therapeutic benefit for PD patients. Here we highlight the concept of MFs re-education as a method of PD therapies, and how we can deploy our knowledge to find out therapeutic regimen for PD treatment.
Acta Scientific Neurology
Amyotrophic lateral sclerosis (ALS) is a motor neuron disease (MND) with the worst prognosis with... more Amyotrophic lateral sclerosis (ALS) is a motor neuron disease (MND) with the worst prognosis with 4-5 years. Both upper and lower motor neurons in the cortex and in the brainstem spinal cord are affected. No effective treatments are available yet. Furthermore, in 10-14% ALS cases are involved with genetic defects, while about 90% cases are reported as sporadic. In fact, immune dysregulation causes the activation of inflammatory cells that augment the ALS disease progression. M2 macrophages have immunosuppressive activity, produces high level of anti-inflammatory cytokine IL-10 and mediates tissue repair, noticed in diabetic and nephrotic mice. The M1-type of macrophages (M s), are pro-inflammatory and causes lung disease, like ALI (acute lung injury) and ARDS (acute respiratory distress syndrome). Recently, it was demonstrated that M2-type of M s are immunosuppressive, can induce boost Tregs (Regulatory T cells), and serves as a candidate for immune-cell-based therapy for ALS. In this review we drew a hypothetical connection, supported by evidence, between nanoparticles medicated M s polarization to M2 type and targeting to deliver in the brain for ALS control.
Integrative Molecular Medicine
Airborne and potentially deadly SARS-CoV-2, that causes the disease COVID-19, was discovered in l... more Airborne and potentially deadly SARS-CoV-2, that causes the disease COVID-19, was discovered in late December of 2019. Till now no medications including vaccine, antibody, or any antiviral are found with success. SARS-CoV-2 is very similar to SARS-CoV-1 which was discovered in 2003, and recognizes the same host cell receptor for entry into the cell. MERS-CoV, another lethal HCoV discovered in 2012, belongs to the same group of SARS (β-type), but recognizes a different cell receptor for host cell entry. All these viruses can only be studied safely under high-level biosafety conditions to protect the laboratory workers and the environment. However, these safety precautions slow down efforts to find drugs and vaccines for COVID-19 since many scientists lack access to the required biosafety facilities. There are four more common human CoVs, such as, HCoV-229E, HCoV-OC43, HCoV-HKU1, and HCoV-NL63, which were known from many years back. They cause self-limiting respiratory infections, such as common cold, in humans, and can be studied safely in BSL2 lab. In this review, a comparison of SARS and Common cold virus were done in order to search for a better surrogate virus those can be used in BSL2 lab for identifying the disease mechanism and therapeutic intervention of SAR-CoV-2. We focused on the following key questions, like, virus-host cell interaction mechanism; the differential cell line susceptibility; species tropism; viral replication efficiency; antigen expression patterns; mechanistic pathway of apoptosis; and structure-function relationship of the virus.
So far, there are seven coronaviruses identified that infect humans and only 4 of them belong to ... more So far, there are seven coronaviruses identified that infect humans and only 4 of them belong to the beta family of coronavirus (HCoV-HKU1, SARS-CoV-2, MERS-CoV and SARS-CoV). SARS family are known to cause severe respiratory disease in humans. In fact, SARS-CoV-2 infection caused a pandemic COVID-19 disease with high morbidity and mortality. Remdesivir (RDV) is the only antiviral drug so far approved for COVID-19 therapy by the FDA. However, the efficacy of RDV in vivo is limited due to its low stability in presence of plasma. This is the report of analysis of the non-clinical pharmacology study of NV-CoV-2 (Polymer) and NV-CoV-2-R (Polymer encapsulated Remdesivir) in both infected and uninfected rats with SARS-CoV-2.Detection and quantification of NV-CoV-2-R in plasma samples was done by MS-HPLC chromatography analyses of precipitated plasma samples from rat subjects.NV-CoV-2-R show RDV peak in MS-HPLC chromatography, whereas only NV-CoV-2 does not show any RDV-Peak, as expected.N...
Search for Therapeutics against COVID-19: A Recent Approach
Recent Developments in Medicine and Medical Research Vol. 13, 2021
Uploads
Papers by Ashok Chakraborty