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1.
Biomacromolecule-based nanocarrier strategies to deliver plant-derived bioactive components for cancer treatment: A recent review.
Gorain, B, Karmakar, V, Sarkar, B, Dwivedi, M, Leong, JTL, Toh, JH, Seah, E, Ling, KY, Chen, KY, Choudhury, H, et al
International journal of biological macromolecules. 2023;(Pt 1):126623
Abstract
The quest for safe chemotherapy has attracted researchers to explore anticancer potential of herbal medicines. Owing to upsurging evidence of herbal drug's beneficial effects, hopes are restored for augmenting survival rates in cancer patients. However, phytoconstituents confronted severe limitations in terms of poor absorption, low-stability, and low bioavailability. Along with toxicity issues associated with phytoconstituents, quality control and limited regulatory guidance also hinder the prevalence of herbal medicines for cancer therapy. Attempts are underway to exploit nanocarriers to circumvent the limitations of existing and new herbal drugs, where biological macromolecules (e.g., chitosan, hyaluronic acid, etc.) are established highly effective in fabricating nanocarriers and cancer targeting. Among the discussed nanocarriers, liposomes and micelles possess properties to cargo hydro- and lipophilic herbal constituents with surface modification for targeted delivery. Majorly, PEG, transferrin and folate are utilized for surface modification to improve bioavailability, circulation time and targetability. The dendrimer and carbon nanotubes responded in high-loading efficiency of phytoconstituent; whereas, SLN and nanoemulsions are suited carriers for lipophilic extracts. This review emphasized unveiling the latent potential of herbal drugs along with discussing on extended benefits of nanocarriers-based delivery of phytoconstituents for safe cancer therapy owing to enhanced clinical and preclinical outcomes without compromising safety.
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2.
MutBLESS: A tool to identify disease-prone sites in cancer using deep learning.
Pandey, M, Gromiha, MM
Biochimica et biophysica acta. Molecular basis of disease. 2023;(6):166721
Abstract
Understanding the molecular basis and impact of mutations at different stages of cancer are long-standing challenges in cancer biology. Identification of driver mutations from experiments is expensive and time intensive. In the present study, we collected the data for experimentally known driver mutations in 22 different cancer types and classified them into six categories: breast cancer (BRCA), acute myeloid leukaemia (LAML), endometrial carcinoma (EC), stomach cancer (STAD), skin cancer (SKCM), and other cancer types which contains 5747 disease prone and 5514 neutral sites in 516 proteins. The analysis of amino acid distribution along mutant sites revealed that the motifs AAA and LR are preferred in disease-prone sites whereas QPP and QF are dominant in neutral sites. Further, we developed a method using deep neural networks to predict disease-prone sites with amino acid sequence-based features such as physicochemical properties, secondary structure, tri-peptide motifs and conservation scores. We obtained an average AUC of 0.97 in five cancer types BRCA, LAML, EC, STAD and SKCM in a test dataset and 0.72 in all other cancer types together. Our method showed excellent performance for identifying cancer-specific mutations with an average sensitivity, specificity, and accuracy of 96.56 %, 97.39 %, and 97.64 %, respectively. We developed a web server for identifying cancer-prone sites, and it is available at https://web.iitm.ac.in/bioinfo2/MutBLESS/index.html. We suggest that our method can serve as an effective method to identify disease-prone sites and assist to develop therapeutic strategies.
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3.
Identification of potential driver mutations in glioblastoma using machine learning.
Pandey, M, Anoosha, P, Yesudhas, D, Gromiha, MM
Briefings in bioinformatics. 2022;(6)
Abstract
Glioblastoma is a fast and aggressively growing tumor in the brain and spinal cord. Mutation of amino acid residues in targets proteins, which are involved in glioblastoma, alters the structure and function and may lead to disease. In this study, we collected a set of 9386 disease-causing (drivers) mutations based on the recurrence in patient samples and experimentally annotated as pathogenic and 8728 as neutral (passenger) mutations. We observed that Arg is highly preferred at the mutant sites of drivers, whereas Met and Ile showed preferences in passengers. Inspecting neighboring residues at the mutant sites revealed that the motifs YP, CP and GRH, are preferred in drivers, whereas SI, IQ and TVI are dominant in neutral. In addition, we have computed other sequence-based features such as conservation scores, Position Specific Scoring Matrices (PSSM) and physicochemical properties, and developed a machine learning-based method, GBMDriver (GlioBlastoma Multiforme Drivers), for distinguishing between driver and passenger mutations. Our method showed an accuracy and AUC of 73.59% and 0.82, respectively, on 10-fold cross-validation and 81.99% and 0.87 in a blind set of 1809 mutants. The tool is available at https://web.iitm.ac.in/bioinfo2/GBMDriver/index.html. We envisage that the present method is helpful to prioritize driver mutations in glioblastoma and assist in identifying therapeutic targets.
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4.
Precision Postbiotics and Mental Health: the Management of Post-COVID-19 Complications.
Pandey, M, Bhati, A, Priya, K, Sharma, KK, Singhal, B
Probiotics and antimicrobial proteins. 2022;(3):426-448
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Abstract
The health catastrophe originated by COVID-19 pandemic construed profound impact on a global scale. However, a plethora of research studies corroborated convincing evidence conferring severity of infection of SARS-CoV-2 with the aberrant gut microbiome that strongly speculated its importance for development of novel therapeutic modalities. The intense exploration of probiotics has been envisaged to promote the healthy growth of the host, and restore intestinal microecological balance through various metabolic and physiological processes. The demystifying effect of probiotics cannot be defied, but there exists a strong skepticism related to their safety and efficacy. Therefore, molecular signature of probiotics termed as "postbiotics" are of paramount importance and there is continuous surge of utilizing postbiotics for enhancing health benefits, but little is explicit about their antiviral effects. Therefore, it is worth considering their prospective role in post-COVID regime that pave the way for exploring the pastoral vistas of postbiotics. Based on previous research investigations, the present article advocates prospective role of postbiotics in alleviating the health burden of viral infections, especially SARS-CoV-2. The article also posits current challenges and proposes a futuristic model describing the concept of "precision postbiotics" for effective therapeutic and preventive interventions that can be used for management of this deadly disease.
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TFE3-associated perivascular epithelioid cell tumor with complete response to mTOR inhibitor therapy: report of first case and literature review.
Purwar, R, Soni, K, Shukla, M, Verma, A, Kumar, T, Pandey, M
World journal of surgical oncology. 2022;(1):62
Abstract
BACKGROUND Perivascular epitheloid cell tumor (PEComas) are characterized by expression of both muscles, most often smooth muscle actin (in ~80% of cases) and melanocytic markers (mainly HMB-45 and Melan A). TFE 3-associated PEComas are new variant which are poorly defined due to their limited reports in literature. These tumors lack response to targeted mTOR inhibitor therapy due to lack of mutation in TSC gene. Hereby, we are reporting a case of TFE3 associated pelvic PEComa showing excellent response to Everolimus. CASE PRESENTATION A 45-year-old female presented with complaint of abdominal mass and bleeding per vaginum for 4 months. She had a history of total abdominal hysterectomy 3 years back in view of abnormal uterine bleeding and exploratory laprotomy 7 months back to remove some pelvic mass. Imaging suggested of ill-defined heterogenous mass of 9.3 x 9.2 x 16 cm involving the uterus, cervix, and upper 1/3 vagina. Multiple omental and peritoneal deposits were also seen, making probable diagnosis of carcinoma endometrium. USG guided biopsy showed cores of fibrous tissue with the presence of cells in sheets with granular eosinophillic cytoplasm; IHC showed positivity for TFE-3, H Caldesmon, GATA-3, and Melan A- and HMB-45; and Ki 67 index was 35%. The basis of above diagnosis of PEComa was made and she was started on Everolimus; repeat imaging after 3 months of therapy showed complete response. CONCLUSION We are reporting first case of malignant pelvic TFE 3 PEComa showing response to mTOR therapy. Identification of TFE 3 PEComa is important because they showed different biologic behavior then their conventional PEComa.
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Advanced drug delivery systems containing herbal components for wound healing.
Gorain, B, Pandey, M, Leng, NH, Yan, CW, Nie, KW, Kaur, SJ, Marshall, V, Sisinthy, SP, Panneerselvam, J, Molugulu, N, et al
International journal of pharmaceutics. 2022;:121617
Abstract
Management of chronic wound has an immense impact on social and economic conditions in the world. Healthcare costs, aging population, physical trauma, and comorbidities of diabetes and obesity seem to be the major factors of this increasing incidence of chronic wounds. Conditions of chronic wound could not restore functional epidermis; thus, delaying the closure of the wound opening in an expected manner. Failures in restoration of skin integrity delay healing due to changes in skin pathology, such as chronic ulceration or nonhealing. The role of different traditional medicines has been explored for use in the healing of cutaneous wounds, where several phytochemicals, such as flavonoids, alkaloids, phenolic acids, tannins are known to provide potential wound healing properties. However, the delivery of plant-based therapeutics could be improved by the novel platform of nanotechnology. Thus, the objectives of novel delivery strategies of principal bioactive from plant sources are to accelerate the wound healing process, avoid wound complications and enhance patient compliance. Therefore, the opportunities of nanotechnology-based drug delivery of natural wound healing therapeutics have been included in the present discussion with special emphasis on nanofibers, vesicular structures, nanoparticles, nanoemulsion, and nanogels.
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7.
Tocotrienol in the Treatment of Topical Wounds: Recent Updates.
Nair, AB, Gorain, B, Pandey, M, Jacob, S, Shinu, P, Aldhubiab, B, Almuqbil, RM, Elsewedy, HS, Morsy, MA
Pharmaceutics. 2022;(11)
Abstract
Healing wounds is an important attempt to keep the internal higher organs safe. Complications in topical wound healing may lead to the formation of scars, which can affect the patient's quality of life. Although several approaches are ongoing in parallel in the exploration of natural compounds via advanced delivery, in this article, an attempt has been made to highlight tocotrienol. Tocotrienol is a natural form of vitamin E and has shown its potential in certain pharmacological activities better than tocopherol. Its antioxidant, anti-inflammatory, cell signal-mediating effects, angiogenic properties, management of scar, and promotion of wound environment with essential factors have shown potential in the management of topical wound healing. Therefore, this review has aimed to focus on recent advances in topical wound healing through the application of tocotrienols. Challenges in delivering tocotrienols to the topical wound due to its large molecular weight and higher logP have also been explored using nanotechnological-based carriers, which has made tocotrienol a potential tool to facilitate the closure of wounds. Exploration of tocotrienol has also been made in human volunteers for biopsy wounds; however, the results are yet to be reported. Overall, based on the current findings in the literature, it could be inferred that tocotrienol would be a viable alternative to the existing wound dressing components for the management of topical wounds.
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Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function.
Michel, M, Benítez-Buelga, C, Calvo, PA, Hanna, BMF, Mortusewicz, O, Masuyer, G, Davies, J, Wallner, O, Sanjiv, K, Albers, JJ, et al
Science (New York, N.Y.). 2022;(6600):1471-1476
Abstract
Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed β,δ-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging.
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9.
Evaluating the beneficial effects of dietary restrictions: A framework for precision nutrigeroscience.
Wilson, KA, Chamoli, M, Hilsabeck, TA, Pandey, M, Bansal, S, Chawla, G, Kapahi, P
Cell metabolism. 2021;(11):2142-2173
Abstract
Dietary restriction (DR) has long been viewed as the most robust nongenetic means to extend lifespan and healthspan. Many aging-associated mechanisms are nutrient responsive, but despite the ubiquitous functions of these pathways, the benefits of DR often vary among individuals and even among tissues within an individual, challenging the aging research field. Furthermore, it is often assumed that lifespan interventions like DR will also extend healthspan, which is thus often ignored in aging studies. In this review, we provide an overview of DR as an intervention and discuss the mechanisms by which it affects lifespan and various healthspan measures. We also review studies that demonstrate exceptions to the standing paradigm of DR being beneficial, thus raising new questions that future studies must address. We detail critical factors for the proposed field of precision nutrigeroscience, which would utilize individualized treatments and predict outcomes using biomarkers based on genotype, sex, tissue, and age.
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Folic Acid Conjugated Nanocarriers for Efficient Targetability and Promising Anticancer Efficacy for Treatment of Breast Cancer: A Review of Recent Updates.
Choudhury, H, Pandey, M, Wen, LP, Cien, LK, Xin, H, Yee, ANJ, Lee, NJ, Gorain, B, Amin, MCIM, Pichika, MR
Current pharmaceutical design. 2020;(42):5365-5379
Abstract
Breast cancer (BC) is the commonest cause of cancer deaths among Women. It is known to be caused due to mutations in certain receptors, viz. estrogens or progesterones. The most frequently used conventional treatment strategies against BC include chemotherapy, radiation therapy, and partial or entire mastectomy, however, these strategies are often associated with multiple adverse effects, thus reducing patient compliance. Advancement of nanotechnology in the medical application has been made to enhance the therapeutic effectiveness with a significant reduction in the unintended side-effects associated with incorporated anticancer drugs against cancer. The surface engineering technology of the nanocarriers is more pronounced in delivering the therapeutics specifically to target cells. Consequently, folic acid, a small molecular ligand for the folate receptor overexpressed cells, has shown immense response in treating BC cells. Folic acid conjugated nanocarriers have shown remarkable efficiency in targeting overexpressed folate receptors on the surface of BC cells. Binding of these target-specific folate-conjugated nanocarriers substantially improves the internalization of chemotherapeutics in BC cells, without much exposing the other parts of the body. Simultaneously, these folate-- conjugated nanocarriers provide imaging for regular monitoring of targeted drug delivery systems and their responses to an anticancer therapy. Therefore, this review demonstrates the potential of folate-conjugated nanotherapeutics for the treatment and theranostic approaches against BC along with the significant challenges to anticancer therapy, and the prospective insights into the clinical importance and effectiveness of folate conjugate nanocarriers.