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Article: Pain in chronic prostatitis and the role of ion channels: a brief overview.

Cyril, Asha Caroline / Jan, Reem Kais / Radhakrishnan, Rajan

2021 Volume 16, Issue 1, Page(s) 50–59

Abstract: Background: Prostatitis is the third most common urologic condition affecting more than half the male population at some point in their lives. There are different categories of prostatitis, of which approximately 90% of cases can be classified under the ...

Abstract	Background: Prostatitis is the third most common urologic condition affecting more than half the male population at some point in their lives. There are different categories of prostatitis, of which approximately 90% of cases can be classified under the National Institute of Health (NIH) type III category (chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)) with no causative agents identified. CP/CPPS is associated with several symptoms, of which the most prominent being chronic pain. Despite its high incidence, pain management in patients with CP/CPPS has been poor, possibly due to the lack of understanding of aetiological factors and mechanisms underlying pain development. Methods: An extensive literature search of published articles on the molecular mechanisms of pain in CP/CPPS was conducted using PubMed and Google Scholar search engines (https://pubmed.ncbi.nlm.nih.gov and https://scholar.google.com). The terms used for the search were: prostatitis, pain mechanism in CP/CPPS, prostatitis pain models, acid-sensing ion channels (ASICs), transient receptor potential vanilloid type 1 (TRPVs), purinergic channels (P2X) in prostatitis pain mechanism and inflammatory mediators in CP/CPPS. The papers were identified based on the title and abstract, and after excluding the articles that did not emphasize the pain mechanism in CP/CPPS. Ninety-five articles (36 review and 59 original research papers) met our criteria and were included in the review. Results: A number of inflammatory mediator molecules and pain channels, including ASICs, transient receptor potential vanilloid channels (TRPVs) and P2Xs have been investigated for their role in prostatitis pain pathology using various animal models. Conclusion: This review summarizes the pain mechanisms in CP/CPPS focusing on the inflammatory mediators, neurotransmitters, pain-transducing ion channels and small animal models developed for studying prostatitis.
Language	English
Publishing date	2021-05-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2670872-3
ISSN	2049-4645 ; 2049-4637
ISSN (online)	2049-4645
ISSN	2049-4637
DOI	10.1177/20494637211015265
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Mechanisms of pain in sickle cell disease.

Takaoka, Kensuke / Cyril, Asha Caroline / Jinesh, Sandhya / Radhakrishnan, Rajan

British journal of pain

2020 Volume 15, Issue 2, Page(s) 213–220

Abstract: Objectives: The hallmark of sickle cell disease (SCD) is acute and chronic pain, and the pain dominates the clinical characteristics of SCD patients. Although pharmacological treatments of SCD targeting the disease mechanisms have been improved, many ... ...

Abstract	Objectives: The hallmark of sickle cell disease (SCD) is acute and chronic pain, and the pain dominates the clinical characteristics of SCD patients. Although pharmacological treatments of SCD targeting the disease mechanisms have been improved, many SCD patients suffer from pain. To overcome the pain of the disease, there have been renewed requirements to understand the novel molecular mechanisms of the pain in SCD. Methods: We concisely summarized the molecular mechanisms of SCD-related acute and chronic pain, focusing on potential drug targets to treat pain. Results: Acute pain of SCD is caused by vaso-occulusive crisis (VOC), impaired oxygen supply or infarction-reperfusion tissue injuries. In VOC, inflammatory cytokines include tryptase activate nociceptors and transient receptor potential vanilloid type 1. In tissue injury, the secondary inflammatory response is triggered and causes further tissue injuries. Tissue injury generates cytokines and pain mediators including bradykinin, and they activate nociceptive afferent nerves and trigger pain. The main causes of chronic pain are from extended hyperalgesia after a VOC and central sensitization. Neuropathic pain could be due to central or peripheral nerve injury, and protein kinase C might be associated with the pain. In central sensitization, neuroplasticity in the brain and the activation of glial cells may be related with the pain. Discussion: In this review, we summarized the molecular mechanisms of SCD-related acute and chronic pain. The novel treatments targeting the disease mechanisms would interrupt complications of SCD and reduce the pain of the SCD patients.
Language	English
Publishing date	2020-05-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2670872-3
ISSN	2049-4645 ; 2049-4637
ISSN (online)	2049-4645
ISSN	2049-4637
DOI	10.1177/2049463720920682
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Statins and Male Fertility: Is There a Cause for Concern?

Omolaoye, Temidayo S / Halabi, Mouhammad Omar / Mubarak, Maitha / Cyril, Asha Caroline / Duvuru, Ruthwik / Radhakrishnan, Rajan / Du Plessis, Stefan S

Toxics

2022 Volume 10, Issue 10

Abstract: The well-known 3-hydroxyl 3-methyl glutaryl-Coenzyme A reductase inhibitors, called statins, have been the main medication used in the treatment of hypercholesterolemia and some cases of cardiovascular diseases. The effectiveness of this drug in ... ...

Abstract	The well-known 3-hydroxyl 3-methyl glutaryl-Coenzyme A reductase inhibitors, called statins, have been the main medication used in the treatment of hypercholesterolemia and some cases of cardiovascular diseases. The effectiveness of this drug in controlling cholesterol production is impeccable, however, patients often complain of a variety of side effects, such as myalgia, muscle atrophy, and in some cases, rhabdomyolysis. Not only has the use of statins caused the aforementioned side effects, but they are also shown to cause testicular discomfort, erectile dysfunction, altered semen parameters, and modified steroid hormone production. These reported adverse effects on male fertility are not generally agreed upon, as some have shown the use to be beneficial. Hence, this makes the aftermath effect of statin use on male fertility debatable and controversial. The negative effects have been associated with imbalanced or reduced steroid hormones, which are necessary for proper spermatogenesis and other sexual functions. Meanwhile, the beneficial effects are related to statin's anti-inflammatory and cardioprotective properties. These contradictory findings are in part due to the different age of users, concentrations of statins, the type and duration of treatment, and the underlying disease and/or comorbidities. Therefore, the current study aims to analyze the literature and gather evidence as to the effects of statin on male sexual health and reproductive parameters, and subsequently give recommendations for the direction of future studies.
Language	English
Publishing date	2022-10-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2733883-6
ISSN	2305-6304 ; 2305-6304
ISSN (online)	2305-6304
ISSN	2305-6304
DOI	10.3390/toxics10100627
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Article ; Online: Nigella sativa and its chemical constituents: pre-clinical and clinical evidence for their potential anti-SARS-CoV-2 effects.

Cyril, Asha Caroline / Ali, Najma Mohamed / Nelliyulla Parambath, Anagha / Vazhappilly, Cijo George / Jan, Reem Kais / Karuvantevida, Noushad / Aburamadan, Haneen / Lozon, Yosra / Radhakrishnan, Rajan

Inflammopharmacology

2023 Volume 32, Issue 1, Page(s) 273–285

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 500 million reported cases of COVID-19 worldwide with relatively high morbidity and mortality. Although global vaccination drive has helped control the pandemic, the newer ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 500 million reported cases of COVID-19 worldwide with relatively high morbidity and mortality. Although global vaccination drive has helped control the pandemic, the newer variant of the virus still holds the world in ransom. Several medicinal herbs with antiviral properties have been reported, and one such promising herb is Nigella sativa (NS). Recent molecular docking, pre-clinical, and clinical studies have shown that NS extracts may have the potential to prevent the entry of coronaviruses into the host cell as well as to treat and manage COVID-19 symptoms. Several active compounds from NS, such as nigelledine, α-hederin, dithymoquinone (DTQ), and thymoquinone (TQ), have been proposed as excellent ligands to target angiotensin-converting enzyme 2 (ACE2 receptors) and other targets on host cells as well as the spike protein (S protein) on SARS-CoV-2. By binding to these target proteins, these ligands could potentially prevent the binding between ACE2 and S protein. Though several articles have been published on the promising therapeutic role of NS and its constituents against SARS-CoV-2 infection, in this review, we consolidate the published information on NS and SARS-CoV-2, focusing on pre-clinical in silico studies as well as clinical trials reported between 2012 and 2023.
MeSH term(s)	SARS-CoV-2 ; COVID-19 ; Nigella sativa ; Angiotensin-Converting Enzyme 2 ; Molecular Docking Simulation
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2023-11-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1080058-x
ISSN	1568-5608 ; 0925-4692
ISSN (online)	1568-5608
ISSN	0925-4692
DOI	10.1007/s10787-023-01385-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Current methodologies to refine bioavailability, delivery, and therapeutic efficacy of plant flavonoids in cancer treatment.

Vazhappilly, Cijo George / Amararathna, Madumani / Cyril, Asha Caroline / Linger, Rebecca / Matar, Rachel / Merheb, Maxime / Ramadan, Wafaa S / Radhakrishnan, Rajan / Rupasinghe, H P Vasantha

The Journal of nutritional biochemistry

2021 Volume 94, Page(s) 108623

Abstract: Over the last two decades, several advancements have been made to improve the therapeutic efficacy of plant flavonoids, especially in cancer treatment. Factors such as low bioavailability, poor flavonoid stability and solubility, ineffective targeted ... ...

Abstract	Over the last two decades, several advancements have been made to improve the therapeutic efficacy of plant flavonoids, especially in cancer treatment. Factors such as low bioavailability, poor flavonoid stability and solubility, ineffective targeted delivery, and chemo-resistance hinder the application of flavonoids in anti-cancer therapy. Many anti-cancer compounds failed in the clinical trials because of unexpected altered clearance of flavonoids, poor absorption after administration, low efficacy, and/or adverse effects. Hence, the current research strategies are focused on improving the therapeutic efficacy of plant flavonoids, especially by enhancing their bioavailability through combination therapy, engineering gut microbiota, regulating flavonoids interaction with adenosine triphosphate binding cassette efflux transporters, and efficient delivery using nanocrystal and encapsulation technologies. This review aims to discuss different methodologies with examples from reported dietary flavonoids that showed an enhanced anti-cancer efficacy in both in vitro and in vivo models. Further, the review discusses the recent progress in biochemical modifications of flavonoids to improve bioavailability, solubility, and therapeutic efficacy.
MeSH term(s)	Antineoplastic Agents, Phytogenic/adverse effects ; Antineoplastic Agents, Phytogenic/chemistry ; Antineoplastic Agents, Phytogenic/pharmacology ; Biological Availability ; Diet ; Drug Delivery Systems ; Flavonoids/adverse effects ; Flavonoids/chemistry ; Flavonoids/pharmacokinetics ; Flavonoids/pharmacology ; Humans ; Neoplasms/drug therapy
Chemical Substances	Antineoplastic Agents, Phytogenic ; Flavonoids
Language	English
Publishing date	2021-03-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1014929-6
ISSN	1873-4847 ; 0955-2863
ISSN (online)	1873-4847
ISSN	0955-2863
DOI	10.1016/j.jnutbio.2021.108623
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Article: Current methodologies to refine bioavailability, delivery, and therapeutic efficacy of plant flavonoids in cancer treatment

Vazhappilly, Cijo George / Amararathna, Madumani / Cyril, Asha Caroline / Linger, Rebecca / Matar, Rachel / Merheb, Maxime / Ramadan, Wafaa S / Radhakrishnan, Rajan / Rupasinghe, H.P. Vasantha

Journal of nutritional biochemistry. 2021 Aug., v. 94

2021

Abstract	Over the last two decades, several advancements have been made to improve the therapeutic efficacy of plant flavonoids, especially in cancer treatment. Factors such as low bioavailability, poor flavonoid stability and solubility, ineffective targeted delivery, and chemo-resistance hinder the application of flavonoids in anti-cancer therapy. Many anti-cancer compounds failed in the clinical trials because of unexpected altered clearance of flavonoids, poor absorption after administration, low efficacy, and/or adverse effects. Hence, the current research strategies are focused on improving the therapeutic efficacy of plant flavonoids, especially by enhancing their bioavailability through combination therapy, engineering gut microbiota, regulating flavonoids interaction with adenosine triphosphate binding cassette efflux transporters, and efficient delivery using nanocrystal and encapsulation technologies. This review aims to discuss different methodologies with examples from reported dietary flavonoids that showed an enhanced anti-cancer efficacy in both in vitro and in vivo models. Further, the review discusses the recent progress in biochemical modifications of flavonoids to improve bioavailability, solubility, and therapeutic efficacy.
Keywords	absorption ; bioavailability ; cancer therapy ; encapsulation ; flavonoids ; intestinal microorganisms ; nanocrystals ; solubility
Language	English
Dates of publication	2021-08
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-light
ZDB-ID	1014929-6
ISSN	1873-4847 ; 0955-2863
ISSN (online)	1873-4847
ISSN	0955-2863
DOI	10.1016/j.jnutbio.2021.108623
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Article: Autoimmune encephalitis: Clinical diagnosis versus antibody confirmation.

Cyril, Asha Caroline / Nair, Sruthi S / Mathai, Annamma / Kannoth, Sudheeran / Thomas, Sanjeev V

Annals of Indian Academy of Neurology

2014 Volume 18, Issue 4, Page(s) 408–411

Abstract: Context: Autoimmune encephalitis is a heterogeneous disorder which is being diagnosed with increasing frequency. The diagnosis of these disorders is based on the detection of autoantibodies and characteristic clinical profiles.: Aims: We aimed to ... ...

Abstract	Context: Autoimmune encephalitis is a heterogeneous disorder which is being diagnosed with increasing frequency. The diagnosis of these disorders is based on the detection of autoantibodies and characteristic clinical profiles. Aims: We aimed to study the antibody profile in encephalitis patients with suspected autoimmune etiology presenting to a tertiary care center. Settings and design: The subjects were selected by screening all patients with clinical profile suggesting autoimmune encephalitis admitted in the neuromedical intensive care unit (ICU) of a tertiary care center in South India. Materials and methods: Patients who fulfilled modified Zuliani et al.'s, criteria for autoimmune encephalitis were identified during the period December 2009-June 2013. Blood samples from these subjects were screened for six neuronal antibodies. Statistical analysis used: Chi-square test was applied to compare the antibody positive and negative patients. Results: Out of 1,227 patients screened, 39 subjects (14 males: 25 females) were identified with a mean age of 15.95 years and 19 cases were assessed in the acute and 20 in the convalescent phase of the illness. Seizure (87.8 %) was the most common presenting symptom; status epilepticus occurred in 23 (60.5%) patients during the course of the illness. Fourteen (35.9%) patients were N-methyl-D-aspartate receptor (NMDAR) antibody-positive and all were negative for the other antibodies tested. Conclusions: One-third of patients presenting with acute noninfective encephalitis would be positive for NMDAR antibodies with the remaining two-thirds with clinically suspected autoimmune encephalitis being antibody-negative. There are few markers in the clinical and investigative profiles to distinguish antibody-positive and -negative patients.
Language	English
Publishing date	2014-12-16
Publishing country	India
Document type	Journal Article
ZDB-ID	2240174-X
ISSN	1998-3549 ; 0972-2327
ISSN (online)	1998-3549
ISSN	0972-2327
DOI	10.4103/0972-2327.165454
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Article ; Online: Autoimmune encephalitis

Asha Caroline Cyril / Sruthi S Nair / Annamma Mathai / Sudheeran Kannoth / Sanjeev V Thomas

Annals of Indian Academy of Neurology, Vol 18, Iss 4, Pp 408-

Clinical diagnosis versus antibody confirmation

2015 Volume 411

Abstract	Context: Autoimmune encephalitis is a heterogeneous disorder which is being diagnosed with increasing frequency. The diagnosis of these disorders is based on the detection of autoantibodies and characteristic clinical profiles. Aims: We aimed to study the antibody profile in encephalitis patients with suspected autoimmune etiology presenting to a tertiary care center. Settings and Design: The subjects were selected by screening all patients with clinical profile suggesting autoimmune encephalitis admitted in the neuromedical intensive care unit (ICU) of a tertiary care center in South India. Materials and Methods: Patients who fulfilled modified Zuliani et al.′s, criteria for autoimmune encephalitis were identified during the period December 2009-June 2013. Blood samples from these subjects were screened for six neuronal antibodies. Statistical analysis used: Chi-square test was applied to compare the antibody positive and negative patients. Results: Out of 1,227 patients screened, 39 subjects (14 males: 25 females) were identified with a mean age of 15.95 years and 19 cases were assessed in the acute and 20 in the convalescent phase of the illness. Seizure (87.8 %) was the most common presenting symptom; status epilepticus occurred in 23 (60.5%) patients during the course of the illness. Fourteen (35.9%) patients were N-methyl-D-aspartate receptor (NMDAR) antibody-positive and all were negative for the other antibodies tested. Conclusions: One-third of patients presenting with acute noninfective encephalitis would be positive for NMDAR antibodies with the remaining two-thirds with clinically suspected autoimmune encephalitis being antibody-negative. There are few markers in the clinical and investigative profiles to distinguish antibody-positive and -negative patients.
Keywords	Autoimmune ; encephalitis ; NMDA antibody ; seizures ; Neurology. Diseases of the nervous system ; RC346-429 ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; Internal medicine ; RC31-1245 ; Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Medknow Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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