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Peptide-based and small molecule PD-1 and PD-L1 pharmacological modulators in the treatment of cancer

Islam MK, Stanslas J

Pharmacol Ther, 2021 11;227:107870.
PMID: 33895183 DOI: 10.1016/j.pharmthera.2021.107870

Cancer immunotherapy is an option to enhance physiological defence mechanism to fight cancer, where natural substances (e.g., antigen/antibody) or small synthetic molecule can be utilized to improve and restore the immune system to stop or slacken the development of malignant cells, stop metastasis and/or help the immune response with synthetic monoclonal antibodies (mAbs) and tumour-agnostic therapy to eliminate cancer cells. Interaction between the programmed cell death ligand 1 (PD-L1) and its receptor (programmed cell death protein 1, PD-1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) linked signalling pathways have been identified as perilous towards the body's immune mechanism in regulating the progression of cancer. It is known that certain cancers use these pathways to evade the body's defence mechanism. The immune system is capable of responding to cancer by stalling these trails with specific synthetic antibodies or immune checkpoint inhibitors, which can ultimately either stop or slow cancer cell development. Recent findings and data suggested that using such inhibitors invigorated a new approach to cancer treatment. These inhibitors usually activate the immune system to identify and eliminate cancer cells rather than attacking tumour cells directly. PD-1/PD-L1 inhibitors have already been substantiated for their efficacy in over twenty variations of cancer through different clinical trials. Studies on molecular interaction with existing PD-1/PD-L1 inhibitors that are mainly dominated by antibodies are constantly generating new ideas to develop novel inhibitors. This review has summarised information on reported and/or patented small molecules and peptides for their ability to interact with the PD-1/PD-L1 as a potential anticancer strategy.
Fulltext Inhibition of VEGF: a novel mechanism to control angiogenesis by Withania somnifera's key metabolite Withaferin A

Saha S, Islam MK, Shilpi JA, Hasan S

In Silico Pharmacol, 2013;1:11.
PMID: 25505656 DOI: 10.1186/2193-9616-1-11

Angiogenesis, or new blood vessel formation from existing one, plays both beneficial and detrimental roles in living organisms in different aspects. Vascular endothelial growth factor (VEGF), a signal protein, well established as key regulator of vasculogenesis and angiogenesis. VEGF ensures oxygen supply to the tissues when blood supply is not adequate, or tissue environment is in hypoxic condition. Limited expression of VEGF is necessary, but if it is over expressed, then it can lead to serious disease like cancer. Cancers that have ability to express VEGF are more efficient to grow and metastasize because solid cancers cannot grow larger than a limited size without adequate blood and oxygen supply. Anti-VEGF drugs are already available in the market to control angiogenesis, but they are often associated with severe side-effects like fetal bleeding and proteinuria in the large number of patients. To avoid such side-effects, new insight is required to find potential compounds as anti-VEGF from natural sources. In the present investigation, molecular docking studies were carried out to find the potentiality of Withaferin A, a key metabolite of Withania somnifera, as an inhibitor of VEGF.
Ecotourism or ecological concerns? Tracing the impact of economic policy uncertainty and natural resources on tourism-driven ecological footprints

Sahoo M, Mohanty PP, Kaushik S, Islam MK, Rourt L

Environ Sci Pollut Res Int, 2024 Apr 17.
PMID: 38630401 DOI: 10.1007/s11356-024-33244-7

The influence of tourism development and economic policy uncertainties on environmental sustainability is substantial. Promoting responsible tourism and using sustainable tourism practises, like offering eco-friendly lodging, is a key part of protecting natural habitats and lowering carbon footprints. Hence, this study tries to examine the relationship between tourism development, economic policy uncertainty, renewable energy, and natural resources on the ecological footprint of India during 1990-2022. This study applies a novel dynamic ARDL simulation approach for long-run and short-run analyses. The study also employs frequency-domain causality to check the causal relationship between the variables. The result reveals that tourism has a positive effect on the ecological footprint. Similarly, economic policy uncertainty has a positive and significant effect on the ecological footprint in India during the sample period. Additionally, natural resource rent shows a positive effect on the ecological footprint or deteriorating environmental quality in the short and long run in the sample period. However, renewable energy consumption indicates a negative effect on the ecological footprint. The results reveal that TDI and EPU have rejected the null hypothesis of no Granger cause in the long, medium, and short term. While renewable energy has a causal relationship with ecological footprints in both the long run and medium run, it is imperative for India to adopt measures that facilitate the advancement of sustainable tourism, with a particular focus on promoting environmentally friendly lodging options, enhancing public transportation systems, and implementing effective waste management strategies.
An ethnobotanical study of medicinal plants used by tribal and native people of Madhupur forest area, Bangladesh

Islam MK, Saha S, Mahmud I, Mohamad K, Awang K, Jamal Uddin S, et al.

J Ethnopharmacol, 2014 Feb 3;151(2):921-30.
PMID: 24342778 DOI: 10.1016/j.jep.2013.11.056

Madhupur forest area, Tangail is one of early human settlements in Bangladesh. Having abode in the vicinity of the forest, a strong ethnobotanical practice has prevailed in this area since ancient time. Due to the rapid deforestation during the last few decades, many plants have already disappeared or are facing extinction. Thus we attempted to document the medicinal plant use of Madhupur forest area with a view to preserve the ethnobotanical knowledge and in order to protect the biodiversity of this area.
Adaptive therapy to circumvent drug resistance to tyrosine kinase inhibitors in cancer: is it clinically relevant?

Faisal Hamdi AI, How SH, Islam MK, Lim JCW, Stanslas J

Expert Rev Anticancer Ther, 2022 Dec;22(12):1309-1323.
PMID: 36376248 DOI: 10.1080/14737140.2022.2147671

INTRODUCTION: Cancer is highly adaptable and is constantly evolving against current targeted therapies such as tyrosine kinase inhibitors. Despite advances in recent decades, the emergence of drug resistance to tyrosine kinase inhibitors constantly hampers therapeutic efficacy of cancer treatment. Continuous therapy versus intermittent clinical regimen has been a debate in drug administration of cancer patients. An ecologically-inspired shift in cancer treatment known as 'adaptive therapy' intends to improve the drug administration of drugs to cancer patients that can delay emergence of drug resistance.
AREAS COVERED: We discuss improved understanding of the concept of drug resistance, the basis of continuous therapy, intermittent clinical regimens, and adaptive therapy will be reviewed. In addition, we discuss how adaptive therapy provides guidance for future cancer treatment.
EXPERT OPINION: The current understanding of drug resistance in cancer leads to poor prognosis and limited treatment options in patients. Fighting drug resistance mutants is constantly followed by new forms of resistance. In most reported cases, continuous therapy leads to drug resistance and an intermittent clinical regimen vaguely delays it. However, adaptive therapy, conceptually, exploits multiple parameters that can suppress the growth of drug resistance and provides safe treatment for cancer patients in the future.
Fulltext Antinociceptive and antioxidant activity of Zanthoxylum budrunga wall (Rutaceae) seeds

Islam MK, Biswas NN, Saha S, Hossain H, Jahan IA, Khan TA, et al.

ScientificWorldJournal, 2014;2014:869537.
PMID: 24707219 DOI: 10.1155/2014/869537

Different parts of the medicinal plant Zanthoxylum budrunga Wall enjoy a variety of uses in ethnobotanical practice in Bangladesh. In the present study, a number of phytochemical and pharmacological investigations were done on the ethanol extract of Z. budrunga seeds (ZBSE) to evaluate its antinociceptive and antioxidant potential. ZBSE was also subjected to HPLC analysis to detect the presence of some common antioxidants. In acetic acid induced writhing test in mice, ZBSE showed 65.28 and 74.30% inhibition of writhing at the doses of 250 and 500 mg/kg and the results were statistically significant (P < 0.001). In hot-plate test, ZBSE raised the pain threshold significantly (P < 0.001) throughout the entire observation period. In DPPH scavenging assay, the IC50 of ZBSE was observed at 82.60 μg/mL. The phenolic content was found to be 338.77 mg GAE/100 g of dried plant material. In reducing power assay, ZBSE showed a concentration dependent reducing ability. HPLC analysis indicated the presence of caffeic acid with a concentration of 75.45 mg/100 g ZBSE. Present investigation supported the use of Zanthoxylum budrunga seed in traditional medicine for pain management. Constituents including caffeic acid and other phenolics might have some role in the observed activity.
The impact of cycleanine in cancer research: a computational study

Nwaefulu ON, Al-Shar'i NA, Owolabi JO, Sagineedu SR, Woei LC, Wai LK, et al.

J Mol Model, 2022 Oct 04;28(11):340.
PMID: 36194315 DOI: 10.1007/s00894-022-05326-1

Cancer is imposing a global health burden because of the steady increase in new cases. Moreover, current anticancer therapeutics are associated with many drawbacks, mainly the emergence of resistance and the severe adverse effects. Therefore, there is a continuous need for developing new anticancer agents with novel mechanisms of action and lower side effects. Natural products have been a rich source of anticancer medication. Cycleanine, a natural product, was reported to exert an antiproliferative effect on ovarian cancer cells by causing apoptosis through activation of caspases 3/7 and cleavage of poly (ADP-ribose) polymerase to form poly (ADP-ribose) polymerase-1 (PARP1). It is well-established that PARP1 is associated with carcinogenesis, and different PARP1 inhibitors are approved as anticancer drugs. In this study, the cytotoxic activity of cycleanine was computationally investigated to determine whether it is a PARP1 inhibitor or a caspase activator. Molecular docking and molecular dynamics (MD) simulations were utilized for this purpose. The results showed that cycleanine has a good binding affinity to PARP1; moreover, MD simulation showed that it forms a stable complex with the enzyme. Consequently, the results showed that cycleanine is a potential inhibitor of the PARP1 enzyme.
Fulltext Ethnomedicinal survey of various communities residing in Garo Hills of Durgapur, Bangladesh

Khan MA, Islam MK, Siraj MA, Saha S, Barman AK, Awang K, et al.

J Ethnobiol Ethnomed, 2015;11:44.
PMID: 26025456 DOI: 10.1186/s13002-015-0033-3

Garo Hills represents one of earliest human habitation in Bangladesh preserving its ancient cultures due to the geographic location. It is situated in the most northern part of Durgapur sub-district having border with Meghalaya of India. Durgapur is rich in ethnic diversity with Garo and Hajong as the major ethnic groups along with Bangalee settlers from the mainstream population. Thus the ethnomedicinal practice in Garo Hills is considered rich as it encompasses three different groups. Present survey was undertaken to compile the medicinal plant usage among the various communities of the Garo Hills.
Capacity development and safety measures for health care workers exposed to COVID-19 in Bangladesh

Nath TK, Paul A, Sikdar D, Mahanta J, Paul S, Amin MR, et al.

BMC Health Serv Res, 2021 Oct 11;21(1):1079.
PMID: 34635110 DOI: 10.1186/s12913-021-07071-2

BACKGROUND: The safety of health care workers (HCWs) in Bangladesh and the factors associated with getting COVID-19 have been infrequently studied. The aim of this study was to address this gap by assessing the capacity development and safety measures of HCWs in Bangladesh who have been exposed to COVID-19 and by identifying the factors associated with respondents' self-reported participation in capacity development trainings and their safety practices.
METHODS: This cross-sectional study was based on an online survey of 811 HCWs working at 39 dedicated COVID-19 hospitals in Bangladesh. A pretested structured questionnaire consisting of questions related to respondents' characteristics, capacity development trainings and safety measures was administered. Binary logistic regressions were run to assess the association between explanatory and dependent variables.
RESULTS: Among the respondents, 58.1% had been engaged for at least 2 months in COVID-19 care, with 56.5% of them attending capacity development training on the use of personal protective equipment (PPE), 44.1% attending training on hand hygiene, and 35% attending training on respiratory hygiene and cough etiquette. Only 18.1% reported having read COVID-19-related guidelines. Approximately 50% of the respondents claimed that there was an inadequate supply of PPE for hospitals and HCWs. Almost 60% of the respondents feared a high possibility of becoming COVID-19-positive. Compared to physicians, support staff [odds ratio (OR) 4.37, 95% confidence interval (CI) 2.25-8.51] and medical technologists (OR 8.77, 95% CI 3.14-24.47) were more exhausted from working in COVID-19 care. Respondents with longer duty rosters were more exhausted, and those who were still receiving infection prevention and control (IPC) trainings were less exhausted (OR 0.54, 95% CI 0.34-0.86). Those who read COVID-19 guidelines perceived a lower risk of being infected by COVID-19 (OR 0.44, 95% CI 0.29-0.67). Compared to the respondents who strongly agreed that hospitals had a sufficient supply of PPE, others who disagreed (OR 2.68, 95% CI 1.31-5.51) and strongly disagreed (OR 5.05, 95% CI 2.15-11.89) had a higher apprehension of infection by COVID-19.
CONCLUSION: The findings indicated a need for necessary support, including continuous training, a reasonable duty roster, timely diagnosis of patients, and an adequate supply of quality PPE.
Fulltext Pretreatment of Blumea lacera leaves ameliorate acute ulcer and oxidative stress in ethanol-induced Long-Evan rat: A combined experimental and chemico-biological interaction

Hossen MA, Reza ASMA, Ahmed AMA, Islam MK, Jahan I, Hossain R, et al.

Biomed Pharmacother, 2021 Mar;135:111211.
PMID: 33421733 DOI: 10.1016/j.biopha.2020.111211

Blumea lacera (Burm.f.) DC. is described as a valuable medicinal plant in various popular systems of medicine. The aim of the experiment reports the in vivo antiulcer activity of methanol extract of Blumea lacera (MEBLL) and in silico studies of bioactive constituents of MEBLL. In this study, fasted Long-Evans rat treated with 80 % ethanol (0.5 mL) to induce gastric ulcer, were pretreated orally with MEBLL at different doses (250 and 500 mg/kg, p.o., b.w) and omeprazole (20 mg/kg, p.o.) and distilled water were used as a reference drug and normal control respectively. In silico activity against gastric H+-K+ATPase enzyme was also studied. The findings demonstrated that the treatment with MEBLL attenuated markedly ulcer and protected the integrity of the gastric mucosa by preventing the mucosal ulceration altered biochemical parameters of gastric juice such total carbohydrate, total protein and pepsin activity. Additionally, the experimental groups significantly (p