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Article ; Online: Interplay of oxidative stress, cellular communication and signaling pathways in cancer

Muhammad Javed Iqbal / Ayesha Kabeer / Zaighum Abbas / Hamid Anees Siddiqui / Daniela Calina / Javad Sharifi-Rad / William C. Cho

Cell Communication and Signaling, Vol 22, Iss 1, Pp 1-

2024 Volume 16

Abstract: Abstract Cancer remains a significant global public health concern, with increasing incidence and mortality rates worldwide. Oxidative stress, characterized by the production of reactive oxygen species (ROS) within cells, plays a critical role in the ... ...

Abstract	Abstract Cancer remains a significant global public health concern, with increasing incidence and mortality rates worldwide. Oxidative stress, characterized by the production of reactive oxygen species (ROS) within cells, plays a critical role in the development of cancer by affecting genomic stability and signaling pathways within the cellular microenvironment. Elevated levels of ROS disrupt cellular homeostasis and contribute to the loss of normal cellular functions, which are associated with the initiation and progression of various types of cancer. In this review, we have focused on elucidating the downstream signaling pathways that are influenced by oxidative stress and contribute to carcinogenesis. These pathways include p53, Keap1-NRF2, RB1, p21, APC, tumor suppressor genes, and cell type transitions. Dysregulation of these pathways can lead to uncontrolled cell growth, impaired DNA repair mechanisms, and evasion of cell death, all of which are hallmark features of cancer development. Therapeutic strategies aimed at targeting oxidative stress have emerged as a critical area of investigation for molecular biologists. The objective is to limit the response time of various types of cancer, including liver, breast, prostate, ovarian, and lung cancers. By modulating the redox balance and restoring cellular homeostasis, it may be possible to mitigate the damaging effects of oxidative stress and enhance the efficacy of cancer treatments. The development of targeted therapies and interventions that specifically address the impact of oxidative stress on cancer initiation and progression holds great promise in improving patient outcomes. These approaches may include antioxidant-based treatments, redox-modulating agents, and interventions that restore normal cellular function and signaling pathways affected by oxidative stress. In summary, understanding the role of oxidative stress in carcinogenesis and targeting this process through therapeutic interventions are of utmost importance in combating various types of ...
Keywords	Oxidative stress ; Reactive oxygen species ; Cancer ; Carcinogenesis mechanisms ; Medicine ; R ; Cytology ; QH573-671
Subject code	610
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Oxidative stress, free radicals and antioxidants

Priya Chaudhary / Pracheta Janmeda / Anca Oana Docea / Balakyz Yeskaliyeva / Ahmad Faizal Abdull Razis / Babagana Modu / Daniela Calina / Javad Sharifi-Rad

Frontiers in Chemistry, Vol

potential crosstalk in the pathophysiology of human diseases

2023 Volume 11

Abstract: Introduction: Free radicals are reactive oxygen species that constantly circulate through the body and occur as a side effect of many reactions that take place in the human body. Under normal conditions, they are removed from the body by antioxidant ... ...

Abstract	Introduction: Free radicals are reactive oxygen species that constantly circulate through the body and occur as a side effect of many reactions that take place in the human body. Under normal conditions, they are removed from the body by antioxidant processes. If these natural mechanisms are disrupted, radicals accumulate in excess and contribute to the development of many diseases.Methodology: Relevant recent information on oxidative stress, free radicals, reactive oxidative species, and natural and synthetic antioxidants was collected by researching electronic databases such as PubMed / Medline, Web of Science, and Science Direct.Results: According to the analysed studies, this comprehensive review provided a recent update on oxidative stress, free radicals and antioxidants and their impact on the pathophysiology of human diseases.Discussion: To counteract the condition of oxidative stress, synthetic antioxidants must be provided from external sources to supplement the antioxidant defense mechanism internally. Because of their therapeutic potential and natural origin, medicinal plants have been reported as the main source of natural antioxidants phytocompounds. Some non-enzymatic phytocompounds such as flavonoids, polyphenols, and glutathione, along with some vitamins have been reported to possess strong antioxidant activities in vivo and in vitro studies. Thus, the present review describes, in brief, the overview of oxidative stress-directed cellular damage and the unction of dietary antioxidants in the management of different diseases. The therapeutic limitations in correlating the antioxidant activity of foods to human health were also discussed.
Keywords	free radicals ; oxidative stress ; pathophysiology ; chronic diseases ; phytochemicals ; antioxidants ; Chemistry ; QD1-999
Subject code	500
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The potential roles of gossypol as anticancer agent

Danijela Paunovic / Jovana Rajkovic / Radmila Novakovic / Jelica Grujic-Milanovic / Reham Hassan Mekky / Dragos Popa / Daniela Calina / Javad Sharifi-Rad

Chinese Medicine, Vol 18, Iss 1, Pp 1-

advances and future directions

2023 Volume 17

Abstract: Abstract Gossypol, a polyphenolic aldehyde derived from cottonseed plants, has seen a transformation in its pharmaceutical application from a male contraceptive to a candidate for cancer therapy. This shift is supported by its recognized antitumor ... ...

Abstract	Abstract Gossypol, a polyphenolic aldehyde derived from cottonseed plants, has seen a transformation in its pharmaceutical application from a male contraceptive to a candidate for cancer therapy. This shift is supported by its recognized antitumor properties, which have prompted its investigation in the treatment of various cancers and related inflammatory conditions. This review synthesizes the current understanding of gossypol as an anticancer agent, focusing on its pharmacological mechanisms, strategies to enhance its clinical efficacy, and the status of ongoing clinical evaluations. The methodological approach to this review involved a systematic search across several scientific databases including the National Center for Biotechnology Information (NCBI), PubMed/MedLine, Google Scholar, Scopus, and TRIP. Studies were meticulously chosen to cover various aspects of gossypol, from its chemical structure and natural sources to its pharmacokinetics and confirmed anticancer efficacy. Specific MeSH terms and keywords related to gossypol’s antineoplastic applications guided the search strategy. Results from selected pharmacological studies indicate that gossypol inhibits the Bcl-2 family of anti-apoptotic proteins, promoting apoptosis in tumor cells. Clinical trials, particularly phase I and II, reveal gossypol’s promise as an anticancer agent, demonstrating efficacy and manageable toxicity profiles. The review identifies the development of gossypol derivatives and novel carriers as avenues to enhance therapeutic outcomes and mitigate adverse effects. Conclusively, gossypol represents a promising anticancer agent with considerable therapeutic potential. However, further research is needed to refine gossypol-based therapies, explore combination treatments, and verify their effectiveness across cancer types. The ongoing clinical trials continue to support its potential, suggesting a future where gossypol could play a significant role in cancer treatment protocols.
Keywords	Gossypol ; Anticancer mechanisms ; Apoptosis ; Proliferation ; Molecular targets ; Mechanisms ; Other systems of medicine ; RZ201-999
Subject code	610
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Anxiolytic-like effect of Urena lobata (L.) in swiss albino mice

Muhammad Torequl Islam / Thoufiqul Alam Riaz / Seyed Abdulmajid Ayatollahi / Javad Sharifi-Rad

Clinical Phytoscience, Vol 7, Iss 1, Pp 1-

2021 Volume 6

Abstract: Abstract Anxiety disorders are general and psychological problems that are also linked to symptoms of depression. This study aimed to investigate the anxiolytic-like effects of Urena lobata L. (MEUL) methanolic extract in different behavioral paradigms ... ...

Abstract	Abstract Anxiety disorders are general and psychological problems that are also linked to symptoms of depression. This study aimed to investigate the anxiolytic-like effects of Urena lobata L. (MEUL) methanolic extract in different behavioral paradigms in Swiss albino mice. For this, after an oral acute toxicity study, adult male mice were treated with MEUL (250 and 500 mg/kg, p.o.) and/or diazepam (2 mg/kg, i.p.), and subjected to a number of behavioral studies. In the open-field test, the number of square field cross, grooming, and rearing, was counted, while in the light/dark and swing test, the time spent in the dark portion and number of swings was calculated, respectively. Additionally, the phytochemical analysis was also done. Results reveal that the MEUL possesses alkaloids, glycosides, flavonoids, phenols, saponins, terpenes (including triterpenes), gums, and reducing sugars. MEUL showed a significant (p < 0.05) anxiolytic-like effect in experimental animals, where it’s dose-dependently modulated the test parameters in an open-field test. The MEUL also increased the light residence time and the number of swings in a dose-dependent manner. A dose of 500 mg/kg of MEUL caused the highest calming effect when combined with the experimental animals’ diazepam group. Taken together, findings expand an understanding of the impact of U. lobata on the central nervous system and show that this plant may be useful for the treatment of disorders associated with anxiety.
Keywords	Urena lobata ; Anxiety ; Mus musculus ; Behavioral study ; Medicine ; R ; Homeopathy ; RX1-681
Subject code	150
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	SpringerOpen
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ethnopharmacological-Based Validation of Polyalthia suberosa Leaf Extract in Neurological, Hyperalgesic, and Hyperactive Gut Disorders Using Animal Models

Ruhul Amin / Cristina Quispe / Jesús Herrera-Bravo / Md. Mizanur Rahman / Radmila Novakovic / Sevgi Durna Daştan / Atul Kabra / Javad Sharifi-Rad

Evidence-Based Complementary and Alternative Medicine, Vol

2022 Volume 2022

Abstract: Polyalthia suberosa (Roxb.) is a plant used to cure coughs, dysentery, fevers, joint aches, rheumatic pain, inflammation, and a variety of skin diseases. The aim of the study was to evaluate the ethyl acetate extract of Polyalthia suberosa (P. suberosa) ... ...

Abstract	Polyalthia suberosa (Roxb.) is a plant used to cure coughs, dysentery, fevers, joint aches, rheumatic pain, inflammation, and a variety of skin diseases. The aim of the study was to evaluate the ethyl acetate extract of Polyalthia suberosa (P. suberosa) leaves and their effects on mice for neuropharmacological, analgesic, and antidiarrheal activities. For neurological studies, the hole cross, hole board, open field, and thiopental sodium-induced sleep duration measurement methodologies were used. The castor oil-induced diarrhea inhibition test was used to assess antidiarrheal action, and the acetic acid-induced writhing inhibition test was used to determine analgesic effectiveness. The extract was given in doses of 250 and 500 mg kg−1 body weight. As a standard drug, diazepam at a dosage of 3 mg kg−1 was used. The extract was also given to groups, and sleep time was measured and recorded. The onset of the anxiolytic effect of the extract at both doses was found to be significant (p < 0.001), and sleep time increased to 273 minutes. For assessing analgesic activity, the extract along with standard diclofenac was administered and found to be 55.02 percent and 64.33 percent, respectively, for the extracts, and diclofenac was found to be 67.44 percent (p < 0.001). For antidiarrheal activity, it was compared with the standard drug, loperamide. The decrease for plant extracts was 50.07 percent and 70.06 percent at 250 mg kg−1 and 500 mg kg−1, respectively, whereas it was 85.01 percent for loperamide (3 mg kg−1) (p < 0.00). In this study, it was found that ethyl acetate extract of Polyalthia suberosa leaves had strong CNS depressant, analgesic, and antidiarrheal activities, which indicates that it may be used in contemporary medicine.
Keywords	Other systems of medicine ; RZ201-999
Subject code	571
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Management of Streptococcus mutans - Candida spp. Oral Biofilms’ Infections

Bahare Salehi / Dorota Kregiel / Gail Mahady / Javad Sharifi-Rad / Natália Martins / Célia F. Rodrigues

Journal of Clinical Medicine, Vol 9, Iss 2, p

Paving the Way for Effective Clinical Interventions

2020 Volume 517

Abstract: Oral diseases are considered the most common noncommunicable diseases and are related to serious local and systemic disorders. Oral pathogens can grow and spread in the oral mucosae and frequently in biomaterials (e.g., dentures or prostheses) under ... ...

Abstract	Oral diseases are considered the most common noncommunicable diseases and are related to serious local and systemic disorders. Oral pathogens can grow and spread in the oral mucosae and frequently in biomaterials (e.g., dentures or prostheses) under polymicrobial biofilms, leading to several disorders such as dental caries and periodontal disease. Biofilms harbor a complex array of interacting microbes, increasingly unapproachable to antimicrobials and with dynamic processes key to disease pathogenicity, which partially explain the gradual loss of response towards conventional therapeutic regimens. New drugs (synthesized and natural) and other therapies that have revealed promising results for the treatment or control of these mixed biofilms are presented and discussed here. A structured search of bibliographic databases was applied to include recent research. There are several promising new approaches in the treatment of Candida spp.− Streptococcus mutans oral mixed biofilms that could be clinically applied in the near future. These findings confirm the importance of developing effective therapies for oral Candida −bacterial infections.
Keywords	oral biofilm ; infection control ; streptococcus mutans ; candida spp ; natural compounds ; antimicrobial resistance ; Medicine ; R
Subject code	610
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Spermidine as a promising anticancer agent

Parteek Prasher / Mousmee Sharma / Sachin Kumar Singh / Monica Gulati / Dinesh Kumar Chellappan / Rashi Rajput / Gaurav Gupta / Alibek Ydyrys / Marzhan Kulbayeva / Ahmad Faizal Abdull Razis / Babagana Modu / Javad Sharifi-Rad / Kamal Dua

Frontiers in Chemistry, Vol

Recent advances and newer insights on its molecular mechanisms

2023 Volume 11

Abstract: Spermidine is a naturally occurring polyamine compound found in semen. It is also found in several plant sources and boasts a remarkable biological profile, particularly with regards to its anticancer properties. Spermidine specifically interferes with ... ...

Abstract	Spermidine is a naturally occurring polyamine compound found in semen. It is also found in several plant sources and boasts a remarkable biological profile, particularly with regards to its anticancer properties. Spermidine specifically interferes with the tumour cell cycle, resulting in the inhibition of tumor cell proliferation and suppression of tumor growth. Moreover, it also triggers autophagy by regulating key oncologic pathways. The increased intake of polyamines, such as spermidine, can suppress oncogenesis and slow the growth of tumors due to its role in anticancer immunosurveillance and regulation of polyamine metabolism. Spermidine/spermine N-1-acetyltransferase (SSAT) plays a critical role in polyamine homeostasis and serves as a diagnostic marker in human cancers. Chemically modified derivatives of spermidine hold great potential for prognostic, diagnostic, and therapeutic applications against various malignancies. This review discusses in detail the recent findings that support the anticancer mechanisms of spermidine and its molecular physiology.
Keywords	spermidine ; polyamines ; anticancer immunosurveillance ; diagnostic marker ; cell proliferation ; anticancer properties ; Chemistry ; QD1-999
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Enhancing chemical and physical stability of pharmaceuticals using freeze-thaw method

Sergio A. Bernal-Chávez / Alejandra Romero-Montero / Héctor Hernández-Parra / Sheila I. Peña-Corona / María L. Del Prado-Audelo / Sergio Alcalá-Alcalá / Hernán Cortés / Lashyn Kiyekbayeva / Javad Sharifi-Rad / Gerardo Leyva-Gómez

Journal of Biological Engineering, Vol 17, Iss 1, Pp 1-

challenges and opportunities for process optimization through quality by design approach

2023 Volume 18

Abstract: Abstract The freeze-thaw (F/T) method is commonly employed during the processing and handling of drug substances to enhance their chemical and physical stability and obtain pharmaceutical applications such as hydrogels, emulsions, and nanosystems (e.g., ... ...

Abstract	Abstract The freeze-thaw (F/T) method is commonly employed during the processing and handling of drug substances to enhance their chemical and physical stability and obtain pharmaceutical applications such as hydrogels, emulsions, and nanosystems (e.g., supramolecular complexes of cyclodextrins and liposomes). Using F/T in manufacturing hydrogels successfully prevents the need for toxic cross-linking agents; moreover, their use promotes a concentrated product and better stability in emulsions. However, the use of F/T in these applications is limited by their characteristics (e.g., porosity, flexibility, swelling capacity, drug loading, and drug release capacity), which depend on the optimization of process conditions and the kind and ratio of polymers, temperature, time, and the number of cycles that involve high physical stress that could change properties associated to quality attributes. Therefore, is necessary the optimization of F/T conditions and variables. The current research regarding F/T is focused on enhancing the formulations, the process, and the use of this method in pharmaceutical, clinical, and biological areas. The present review aims to discuss different studies related to the impact and effects of the F/T process on the physical, mechanical, and chemical properties (porosity, swelling capacity) of diverse pharmaceutical applications with an emphasis on their formulation properties, the method and variables used, as well as challenges and opportunities in developing. Finally, we review the experimental approach for choosing the standard variables studied in the F/T method applying the systematic methodology of quality by design.
Keywords	Drug substances ; Chemical stability ; Physical stability ; Hydrogels ; Chemical properties ; Pharmaceutical applications ; Biology (General) ; QH301-705.5
Subject code	620
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: TRPM2-mediated Ca2+ signaling as a potential therapeutic target in cancer treatment

Eunus S. Ali / Brototi Chakrabarty / Sarker Ramproshad / Banani Mondal / Neloy Kundu / Chandan Sarkar / Javad Sharifi-Rad / Daniela Calina / William C. Cho

Cell Communication and Signaling, Vol 21, Iss 1, Pp 1-

an updated review of its role in survival and proliferation of cancer cells

2023 Volume 13

Abstract: Abstract 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 ... ...

Abstract	Abstract 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
Keywords	TRPM2 ion channel ; Ca2+ signaling ; Oxidative stress ; Cancer ; Therapeutic target ; Medicine ; R ; Cytology ; QH573-671
Subject code	570
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: LncRNA SNHG6 role in clinicopathological parameters in cancers

Khushbukhat Khan / Muhammad Irfan / Areej Abdul Sattar / Manal Bint Faiz / Anees ur Rahman / Hafsa Athar / Daniela Calina / Javad Sharifi-Rad / William C. Cho

European Journal of Medical Research, Vol 28, Iss 1, Pp 1-

2023 Volume 18

Abstract: Abstract RNA sequencing has revealed that a substantial portion of the human genome undergoes transcription, yet a minimal fraction of these transcripts translates into proteins. LncRNAs, RNA molecules less than 200 nt in length, once deemed as ... ...

Abstract	Abstract RNA sequencing has revealed that a substantial portion of the human genome undergoes transcription, yet a minimal fraction of these transcripts translates into proteins. LncRNAs, RNA molecules less than 200 nt in length, once deemed as transcriptional noise, have now emerged as crucial regulators of numerous cellular processes. This review focuses on the lncRNA SNHG6, aiming to elucidate its biogenesis, the pivotal roles it plays, and its mechanisms in facilitating the hallmarks of cancer. A comprehensive literature review and analysis were undertaken to delve into the biogenesis of SNHG6, its roles in cellular processes, and the mechanisms through which it contributes to the hallmarks of cancer. SNHG6 is a notable lncRNA, observed to be overexpressed in various cancer types; its perturbation has been linked to tumor progression, emphasizing its significance in oncogenesis. This lncRNA contributes to a range of cellular aberrations, influencing transcriptional, post-transcriptional, and epigenetic processes of mRNA, ultimately driving cancerous transformations. LncRNA SNHG6 serves as a potential biomarker and therapeutic target due to its association with tumorigenesis. Understanding its mechanism and role in cancer can pave the way for novel diagnostic and therapeutic strategies.
Keywords	LncRNA ; SNHG6 ; Cancer ; Oncogenes ; Epigenetic control ; Signal transduction ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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