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Article: Noninfectious complications of peritoneal dialysis.

Saha, Tapasi C / Singh, Harmeet

2007 Volume 100, Issue 1, Page(s) 54–58

Abstract: Peritoneal dialysis is an established form of renal replacement therapy. With its increasing popularity, we are now encountering a variety of complications. Noninfectious complications are usually less common as compared with infectious complications. In ...

Abstract	Peritoneal dialysis is an established form of renal replacement therapy. With its increasing popularity, we are now encountering a variety of complications. Noninfectious complications are usually less common as compared with infectious complications. In this review, we discuss some of the common noninfectious complications of peritoneal dialysis such as hernias, hydrothorax, hemoperitoneum, pancreatitis, ischemic colitis and necrotizing enterocolitis, pneumoperitoneum, GERD, subcapsular steatosis and hypokalemia. The awareness of these complications will help in early diagnosis and treatment.
MeSH term(s)	Gastrointestinal Diseases/epidemiology ; Gastrointestinal Diseases/etiology ; Hernia/epidemiology ; Hernia/etiology ; Humans ; Hydrothorax/epidemiology ; Hydrothorax/etiology ; Hypokalemia/epidemiology ; Hypokalemia/etiology ; Incidence ; Kidney Failure, Chronic/therapy ; Pancreatitis/epidemiology ; Pancreatitis/etiology ; Peritoneal Dialysis/adverse effects ; Peritoneal Diseases/epidemiology ; Peritoneal Diseases/etiology ; Prognosis ; Risk Factors
Language	English
Publishing date	2007-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	185329-6
ISSN	1541-8243 ; 0038-4348
ISSN (online)	1541-8243
ISSN	0038-4348
DOI	10.1097/01.smj.0000253477.82103.a6
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Article: Minimal change disease: a review.

Saha, Tapasi C / Singh, Harmeet

Southern medical journal

2006 Volume 99, Issue 11, Page(s) 1264–1270

Abstract: Minimal change disease (MCD) is a histopathological lesion in the kidney that is most commonly associated with nephrotic syndrome. The majority of the cases are idiopathic. Pathogenesis is not well understood, although T-cell-related mechanisms are ... ...

Abstract	Minimal change disease (MCD) is a histopathological lesion in the kidney that is most commonly associated with nephrotic syndrome. The majority of the cases are idiopathic. Pathogenesis is not well understood, although T-cell-related mechanisms are implicated. Massive proteinuria leads to hypoalbuminemia, salt retention, disorder of hemostasis, hyperlipidemia and increased susceptibility to infections. Renal biopsy remains the gold standard for diagnosis. MCD is highly responsive to corticosteroids. Other immunosuppressive agents such as cyclophosphamide, cyclosporin, azathioprine and mycophenolate mofetil have been used to treat cases which are resistant to steroids.
MeSH term(s)	Animals ; Hemostasis ; Humans ; Kidney Glomerulus/physiopathology ; Nephrosis, Lipoid/diagnosis ; Nephrosis, Lipoid/drug therapy ; Nephrosis, Lipoid/pathology ; Nephrosis, Lipoid/physiopathology ; Prognosis ; Proteinuria/physiopathology ; Sodium Chloride/metabolism ; T-Lymphocytes/physiology
Chemical Substances	Sodium Chloride (451W47IQ8X)
Language	English
Publishing date	2006-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	185329-6
ISSN	1541-8243 ; 0038-4348
ISSN (online)	1541-8243
ISSN	0038-4348
DOI	10.1097/01.smj.0000243183.87381.c2
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Article ; Online: NLGP regulates RGS5-TGFβ axis to promote pericyte-dependent vascular normalization during restricted tumor growth.

Dasgupta, Shayani / Saha, Akata / Ganguly, Nilanjan / Bhuniya, Avishek / Dhar, Sukanya / Guha, Ipsita / Ghosh, Tithi / Sarkar, Anirban / Ghosh, Sarbari / Roy, Kamalika / Das, Tapasi / Banerjee, Saptak / Pal, Chiranjib / Baral, Rathindranath / Bose, Anamika

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2022 Volume 36, Issue 5, Page(s) e22268

Abstract: Altered RGS5-associated intracellular pericyte signaling and its abnormal crosstalk with endothelial cells (ECs) result chaotic tumor-vasculature, prevent effective drug delivery, promote immune-evasion and many more to ensure ultimate tumor progression. ...

Abstract	Altered RGS5-associated intracellular pericyte signaling and its abnormal crosstalk with endothelial cells (ECs) result chaotic tumor-vasculature, prevent effective drug delivery, promote immune-evasion and many more to ensure ultimate tumor progression. Moreover, the frequency of lethal-RGS5
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes ; Endothelial Cells ; Glycoproteins ; Mice ; Neoplasms ; Pericytes ; Phosphatidylinositol 3-Kinases ; RGS Proteins ; Transforming Growth Factor beta ; Tumor Microenvironment
Chemical Substances	Glycoproteins ; RGS Proteins ; Rgs5 protein, mouse ; Transforming Growth Factor beta
Language	English
Publishing date	2022-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202101093R
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Article ; Online: Fluorene-induced stress in the benthic oligochaete Tubifex tubifex: A multi-biomarker assessment of toxicological pathways and mechanisms under acute and subchronic exposures.

Sharma, Pramita / Chukwuka, Azubuike Victor / Chatterjee, Soumendranath / Bhowmick, Shovonlal / Mistri, Tapan Kumar / Chandra Saha, Nimai

Chemosphere

2024 Volume 352, Page(s) 141412

Abstract: ... with cytochrome c oxidase suggested interference with cellular energy production. Generalized Read-Across (GenRA) analysis ...

Abstract	This study examined the multifaceted impacts of fluorene exposure on Tubifex tubifex, encompassing acute (survival analysis and behavioral responses) and subchronic exposure regimens (antioxidant enzyme response and histopathology), molecular docking studies, and generalized read-across analysis. Survival analysis revealed concentration-dependent increases in toxicity over varying time intervals, with LC50 values decreasing from 30.072 mg/L at 24 h to 12.365 mg/L at 96 h, emphasizing the time-sensitive and concentration-responsive nature of the stressor. Behavioral responses were both concentration- and duration-dependent. While Erratic Movement and Clumping Tendency exhibited earlier responses (within 24 h) at lower concentrations, the wrinkling effect and mucus secretion) exhibited delayed onset, suggesting intricate regulatory mechanisms underlying adaptability to environmental challenges; moreover, the wrinkling effect was consistently induced at higher concentrations, indicating greater sensitivity to the toxic effects of fluorene. With sublethal environmentally relevant concentrations-1.24 mg/l and 2.47 mg/L i.e., 10% and 20% 96 h, respectively-the antioxidant enzyme response (i.e., upregulation of SOD, CAT, and GST) with increasing fluorene concentration, revealing a nonlinear, hormetic response, suggested adaptive protection at lower doses but inhibition at higher concentrations. Histopathological examination indicated that higher fluorene concentrations caused cellular proliferation, inflammation, and severe tissue damage in the digestive tract and body wall. Molecular docking studies demonstrated robust interactions between fluorene and major stress biomarker enzymes, disrupting their functions and inducing oxidative stress. Interactions with cytochrome c oxidase suggested interference with cellular energy production. Generalized Read-Across (GenRA) analysis unveiled shared toxicity mechanisms among fluorene and its analogs, involving the formation of reactive epoxides and the influence of cytochrome P450 enzymes. The diverse functional groups of these analogs, particularly chlorine-containing compounds, were implicated in toxicity through lipid peroxidation and membrane damage. Adverse outcome pathways and broader consequences for aquatic ecosystem health are discussed.
MeSH term(s)	Animals ; Antioxidants/metabolism ; Ecosystem ; Molecular Docking Simulation ; Oligochaeta ; Biomarkers/metabolism ; Fluorenes/toxicity ; Fluorenes/metabolism ; Water Pollutants, Chemical/metabolism
Chemical Substances	Antioxidants ; Biomarkers ; Fluorenes ; Water Pollutants, Chemical
Language	English
Publishing date	2024-02-07
Publishing country	England
Document type	Journal Article
ZDB-ID	120089-6
ISSN	1879-1298 ; 0045-6535 ; 0366-7111
ISSN (online)	1879-1298
ISSN	0045-6535 ; 0366-7111
DOI	10.1016/j.chemosphere.2024.141412
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Article: Correlation of Maternal Thyroid Stimulating Hormone Levels With Lipid Profile in Pregnant Women With Hypothyroidism.

Yadav, Alka / Katyal, Ranjan / Mittal, Shilpa / Kumar Saha, Tapan

Cureus

2023 Volume 15, Issue 4, Page(s) e37748

Abstract: ... between TSH and Total Cholesterol, Triglycerides, and LDL-C in both the 2nd and 3rd trimesters ... between TSH levels and HDL-C in either trimester. The correlation coefficient and p-value for TSH & HDL ...

Abstract	Introduction Pregnancy leads to changes in hormonal levels and lipid profile. Thyroid hormones play a crucial role in embryonic growth and fetal development. Untreated thyroid disease during pregnancy can lead to a high risk of complications. Aim The aim of the study is to examine the correlation between thyroid stimulating hormone (TSH) and lipid profile in pregnant women with hypothyroidism. Materials and methods This cross-sectional case-control study was conducted at the Biochemistry Department, Alfalah School of Medical Science & Research Centre, Dhauj, Faridabad, Haryana, India. The study consisted of 500 patients (250 cases and 250 controls) who fulfilled the inclusion and exclusion criteria. Of the 250 cases recruited, 23 cases were in the 2nd trimester and 209 cases were in the 3rd trimester. Blood samples were collected from the participants to assess their lipid profile and TSH levels. Results The study showed a statistically significant difference between the mean TSH levels of hypothyroid pregnant females in the 2nd trimester (3.85 ± 0.59) and the 3rd trimester (4.71 ± 0.54). There was a significant positive correlation observed between TSH and Total Cholesterol, Triglycerides, and LDL-C in both the 2nd and 3rd trimesters. In the second trimester, there was a significant positive correlation observed between TSH & TC (r = 0.6634, p<0.0005), TSH & TG (r= 0.7346, p=0.00006), TSH & LDL (r= 0.5322, p= 0.008). In the third trimester, there was a significant positive correlation observed between TSH & TC (r = 0.8929, p<0.00001), TSH & TG (r= 0.430, p<0.00001), TSH & LDL (r= 0.168, p= 0.015). However, no significant correlation was found between TSH levels and HDL-C in either trimester. The correlation coefficient and p-value for TSH & HDL were r = 0.2083, p=0.340 in the second trimester, and r = 0.0189, p=0.2384 in the third trimester. Conclusion A significant increase in TSH levels in hypothyroid pregnant women was observed in the 3rd trimester compared to the second trimester. Moreover, a significant positive correlation was found between TSH and lipid profile (total cholesterol, triglycerides, and LDL) in both trimesters, but not with HDL. These findings highlight the importance of monitoring thyroid hormone levels in the later stages of pregnancy to avoid potential maternal & fetal complications.
Language	English
Publishing date	2023-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.37748
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Article ; Online: Neem leaf glycoprotein binding to Dectin-1 receptors on dendritic cell induces type-1 immunity through CARD9 mediated intracellular signal to NFκB.

Ganguly, Nilanjan / Das, Tapasi / Bhuniya, Avishek / Guha, Ipsita / Chakravarti, Mohona / Dhar, Sukanya / Sarkar, Anirban / Bera, Saurav / Dhar, Jesmita / Dasgupta, Shayani / Saha, Akata / Ghosh, Tithi / Das, Juhina / Sk, Ugir Hossain / Banerjee, Saptak / Laskar, Subrata / Bose, Anamika / Baral, Rathindranath

Cell communication and signaling : CCS

2024 Volume 22, Issue 1, Page(s) 237

Abstract: ... immunomodulation, aid cytotoxic T cell (T: Methods: Six glycoprotein-binding C-type lectins found on APCs ...

Abstract	Background: A water-soluble ingredient of mature leaves of the tropical mahogany 'Neem' (Azadirachta indica), was identified as glycoprotein, thus being named as 'Neem Leaf Glycoprotein' (NLGP). This non-toxic leaf-component regressed cancerous murine tumors (melanoma, carcinoma, sarcoma) recurrently in different experimental circumstances by boosting prime antitumor immune attributes. Such antitumor immunomodulation, aid cytotoxic T cell (T Methods: Six glycoprotein-binding C-type lectins found on APCs, namely, MBR, Dectin-1, Dectin-2, DC-SIGN, DEC205 and DNGR-1 were screened on bone marrow-derived dendritic cells from C57BL/6 J mice. Fluorescence microscopy, RT-PCR, flow cytometry and ELISA revealed Dectin-1 as the NLGP-binding receptor, followed by verifications through RNAi. Following detection of β-Glucans in NLGP, their interactions with Dectin-1 were explored in silico. Roles of second messengers and transcription factors in the downstream signal were studied by co-immunoprecipitation, western blotting, and chromatin-immunoprecipitation. Intracellularization of FITC-coupled NLGP was observed by processing confocal micrographs of DCs. Results: Considering extents of hindrance in NLGP-driven transcription rates of the cytokines IL-10 and IL-12p35 by receptor-neutralization, Dectin-1 receptors on dendritic cells were found to bind NLGP through the ligand's peripheral β-Glucan chains. The resulting signal phosphorylates PKCδ, forming a trimolecular complex of CARD9, Bcl10 and MALT1, which in turn activates the canonical NFκB-pathway of transcription-regulation. Consequently, the NFκB-heterodimer p65:p50 enhances Il12a transcription and the p50:p50 homodimer represses Il10 transcription, bringing about a cytokine-based systemic-bias towards type-1 immune environment. Further, NLGP gets engulfed within dendritic cells, possibly through endocytic activities of Dectin-1. Conclusion: NLGP's binding to Dectin-1 receptors on murine dendritic cells, followed by the intracellular signal, lead to NFκB-mediated contrasting regulation of cytokine-transcriptions, initiating a pro-inflammatory immunopolarization, which amplifies further by the responding immune cells including T
MeSH term(s)	Animals ; Lectins, C-Type/metabolism ; Lectins, C-Type/genetics ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Plant Leaves ; Signal Transduction ; Azadirachta/chemistry ; Mice, Inbred C57BL ; Mice ; CARD Signaling Adaptor Proteins/metabolism ; NF-kappa B/metabolism ; Protein Binding
Chemical Substances	Lectins, C-Type ; dectin 1 ; CARD Signaling Adaptor Proteins ; NF-kappa B ; Card9 protein, mouse
Language	English
Publishing date	2024-04-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2126315-2
ISSN	1478-811X ; 1478-811X
ISSN (online)	1478-811X
ISSN	1478-811X
DOI	10.1186/s12964-024-01576-z
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Article ; Online: An overview of diarrhea among infants and under-five in Punjab-Pakistan.

Jabeen, Saher / Saha, Unnati Rani / van Wesenbeeck, C F A / Mushtaq, Khalid

Journal of pediatric nursing

2023 Volume 71, Page(s) e28–e37

Abstract: ... of factors that result in diarrhea. Hence, improving the source of drinking water, e.g., tap water and ...

Abstract	Background: Diarrhea, pneumonia, malnutrition, tuberculosis, measles, and fever are the leading causes of mortality in children under five-years of age (0-59 months), whereas diarrhea alone is the world's second-biggest cause of mortality in this population. This study is particularly important for Pakistan as it focuses on one of the main causes of infant mortality, diarrhea, which is a major challenge for Pakistan to achieve the Sustainable Development Goals to reduce infant mortality to 12/1000 live births by 2030. Aim: This study was planned to investigate the various household, parental, environmental, and child-related factors causing diarrheal diseases in children aged 0-59 months in Punjab Pakistan. Methods: The study used the data of 38,405 households from the Multiple Indicator Cluster Survey (MICS) 2017-18, directed by the Punjab Bureau of Statistics. Comprehensive descriptive statistics, i.e., cross-tabulations and logistic regression were used for the detailed analysis. Findings: The results showed that infants are more probable to get diarrhea than older children. A wide range of influences were found to affect the probability of a child getting diarrhea, including child-specific, mother-specific and environment-specific ones. One prominent finding was that, at the mother level, the education of the mother played a significant role in reducing diarrhea among children under five-years of age (0-59 months). Discussion: The results of the study contribute to the literature by highlighting that it is an interplay of factors that result in diarrhea. Hence, improving the source of drinking water, e.g., tap water and bottled water, can decrease the occurrence of diarrhea, especially in poor households. It was also revealed that households with a toilet facility of flush have less probability of their children being diagnosed with diarrhea than toilet facilities in open drains and fields. On the child level, results suggested that birth order matters as well, with the firstborn child having a lower probability of contracting diarrhea than siblings born after. Application to practice: Interventions targeting infants and mothers of infants aimed at reducing diarrhea are expected to be very effective to reduce child mortality, one of the main child health challenges faced by Pakistan.
MeSH term(s)	Female ; Infant ; Humans ; Child ; Adolescent ; Child, Preschool ; Pakistan/epidemiology ; Infant Mortality ; Diarrhea/epidemiology ; Surveys and Questionnaires ; Logistic Models
Language	English
Publishing date	2023-04-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	632731-x
ISSN	1532-8449 ; 0882-5963
ISSN (online)	1532-8449
ISSN	0882-5963
DOI	10.1016/j.pedn.2023.04.011
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Zs.MO 375: Show issues

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Article ; Online: LAMP2A overexpression in breast tumors promotes cancer cell survival via chaperone-mediated autophagy.

Saha, Tapas

Autophagy

2012 Volume 8, Issue 11, Page(s) 1643–1656

Abstract: Lysosome-associated membrane protein type 2A (LAMP2A) is a key protein in the chaperone-mediated autophagy (CMA) pathway. LAMP2A helps in lysosomal uptake of modified and oxidatively damaged proteins directly into the lumen of lysosomes for degradation ... ...

Abstract	Lysosome-associated membrane protein type 2A (LAMP2A) is a key protein in the chaperone-mediated autophagy (CMA) pathway. LAMP2A helps in lysosomal uptake of modified and oxidatively damaged proteins directly into the lumen of lysosomes for degradation and protein turnover. Elevated expression of LAMP2A was observed in breast tumor tissues of all patients under investigation, suggesting a survival mechanism via CMA and LAMP2A. Reduced expression of the CMA substrates, GAPDH and PKM, was observed in most of the breast tumor tissues when compared with the normal adjacent tissues. Reactive oxygen species (ROS) mediated oxidative stress damages regulatory cellular components such as DNA, proteins and/or lipids. Protein carbonyl content (PCC) is widely used as a measure of total protein oxidation in cells. Ectopic expression of LAMP2A reduces PCC and thereby promotes cell survival during oxidative stress. Furthermore, inhibition of LAMP2A stimulates accumulation of GAPDH, AKT1 phosphorylation, generation of ROS, and induction of cellular apoptosis in breast cancer cells. Doxorubicin, which is a chemotherapeutic drug, often becomes ineffective against tumor cells with time due to chemotherapeutic resistance. Breast cancer cells deficient of LAMP2A demonstrate increased sensitivity to the drug. Thus, inhibiting CMA activity in breast tumor cells can be exploited as a potential therapeutic application in the treatment of breast cancer.
MeSH term(s)	Apoptosis/drug effects ; Autophagy/drug effects ; Breast Neoplasms/enzymology ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Survival/drug effects ; Cytoprotection/drug effects ; DNA Damage ; Down-Regulation/drug effects ; Doxorubicin/pharmacology ; Female ; Gene Knockdown Techniques ; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)/metabolism ; Half-Life ; Humans ; Lysosomal-Associated Membrane Protein 2 ; Lysosomal Membrane Proteins/antagonists & inhibitors ; Lysosomal Membrane Proteins/metabolism ; Molecular Chaperones/metabolism ; Oxidation-Reduction/drug effects ; Oxidative Stress/drug effects ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Carbonylation/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; Substrate Specificity/drug effects
Chemical Substances	LAMP2 protein, human ; Lysosomal-Associated Membrane Protein 2 ; Lysosomal Membrane Proteins ; Molecular Chaperones ; Reactive Oxygen Species ; Doxorubicin (80168379AG) ; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) (EC 1.2.1.12) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2012-08-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.4161/auto.21654
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Article ; Online: Genome-wide identification and development of miniature inverted-repeat transposable elements and intron length polymorphic markers in tea plant (Camellia sinensis).

Rohilla, Megha / Mazumder, Abhishek / Saha, Dipnarayan / Pal, Tarun / Begam, Shbana / Mondal, Tapan Kumar

Scientific reports

2022 Volume 12, Issue 1, Page(s) 16233

Abstract: ... assamica (CSA) and C. sinensis var. sinensis (CSS) to identify the markers to differentiate tea genotypes ...

Abstract	Marker-assisted breeding and tagging of important quantitative trait loci for beneficial traits are two important strategies for the genetic improvement of plants. However, the scarcity of diverse and informative genetic markers covering the entire tea genome limits our ability to achieve such goals. In the present study, we used a comparative genomic approach to mine the tea genomes of Camellia sinensis var. assamica (CSA) and C. sinensis var. sinensis (CSS) to identify the markers to differentiate tea genotypes. In our study, 43 and 60 Camellia sinensis miniature inverted-repeat transposable element (CsMITE) families were identified in these two sequenced tea genomes, with 23,170 and 37,958 putative CsMITE sequences, respectively. In addition, we identified 4912 non-redundant, Camellia sinensis intron length polymorphic (CsILP) markers, 85.8% of which were shared by both the CSS and CSA genomes. To validate, a subset of randomly chosen 10 CsMITE markers and 15 CsILP markers were tested and found to be polymorphic among the 36 highly diverse tea genotypes. These genome-wide markers, which were identified for the first time in tea plants, will be a valuable resource for genetic diversity analysis as well as marker-assisted breeding of tea genotypes for quality improvement.
MeSH term(s)	Camellia sinensis/genetics ; DNA Transposable Elements/genetics ; Genetic Markers ; Humans ; Introns/genetics ; Plant Breeding ; Tea
Chemical Substances	DNA Transposable Elements ; Genetic Markers ; Tea
Language	English
Publishing date	2022-09-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-20400-7
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Article ; Online: Therapeutic advancements in targeting BCL-2 family proteins by epigenetic regulators, natural, and synthetic agents in cancer.

Sarkar, Arnab / Paul, Abhik / Banerjee, Tanmoy / Maji, Avik / Saha, Sanjukta / Bishayee, Anupam / Maity, Tapan Kumar

European journal of pharmacology

2023 Volume 944, Page(s) 175588

Abstract: Cancer is amongst the deadliest and most disruptive disorders, having a much higher death rate than other diseases worldwide. Human cancer rates continue to rise, thereby posing the most significant concerns for medical health professionals. In the last ... ...

Abstract	Cancer is amongst the deadliest and most disruptive disorders, having a much higher death rate than other diseases worldwide. Human cancer rates continue to rise, thereby posing the most significant concerns for medical health professionals. In the last two decades, researchers have gone past several milestones in tackling cancer while gaining insight into the role of apoptosis in cancer or targeting various biomarker tools for prognosis and diagnosis. Apoptosis which is still a topic full of complexities, can be controlled considerably by B-cell lymphoma 2 (BCL-2) and its family members. Therefore, targeting proteins of this family to prevent tumorigenesis, is essential to focus on the pharmacological features of the anti-apoptotic and pro-apoptotic members, which will help to develop and manage this disorder. This review deals with the advancements of various epigenetic regulators to target BCL-2 family proteins, including the mechanism of several microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Similarly, a rise in natural and synthetic molecules' research over the last two decades has allowed us to acquire insights into understanding and managing the transcriptional alterations that have led to apoptosis and treating various neoplastic diseases. Furthermore, several inhibitors targeting anti-apoptotic proteins and inducers or activators targeting pro-apoptotic proteins in preclinical and clinical stages have been summarized. Overall, agonistic and antagonistic mechanisms of BCL-2 family proteins conciliated by epigenetic regulators, natural and synthetic agents have proven to be an excellent choice in developing cancer therapeutics.
MeSH term(s)	Humans ; Apoptosis ; Apoptosis Regulatory Proteins/metabolism ; Epigenesis, Genetic ; Neoplasms/drug therapy ; Proto-Oncogene Proteins c-bcl-2/metabolism
Chemical Substances	Apoptosis Regulatory Proteins ; Proto-Oncogene Proteins c-bcl-2 ; BCL2 protein, human
Language	English
Publishing date	2023-02-13
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/j.ejphar.2023.175588
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