bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardial Protection with the ATP-Sensitive Potassium Channel Openers
Authors: Atwal Karnail S. 
Published: March 2022

Abstract:
The ATP-sensitive potassium channel (KArP) openers (e.g., Cromakalim) were originally developed for the treatment of hypertension, primarily due to their potent peripheral vasodilating properties. However, the clinical studies have failed to demonstrate any advantage of these compounds over the more established antihypertensive agents. Experimen­ tal studies have shown that the KArP openers may be effective for the treat­
ment of a variety of diseases (asthma, urinary incontinence, ischemia etc.) besides
hypertension. However, their clinical utility is limited due to lack of tissue selectivity. We have shown that KArP openers have direct cardioprotective properties which do ,!lOt require contribution from vasodilation. However, the first generation agents offer a narrow window of safety for the treatment of myocardial ischemia due to their potent peripheral vasodilating properties which can compromise the tissue already at risk. Our efforts to find cardioprotective KArP openers with a lower degree of vasorelaxant potency relative to the first generation agents have resulted in the identification of a new class of agents (5). Their structure-activity relationships for antiischemic activity and efficacy in vivo are summarized in this review. The structure-activity studies show that an electron withdrawing group at C6 of the benzopyran ring, a gem-dimethyl at C2, a trans-hydroxyl at C3, an sp3 carbon at C3/C4 and an aryl ring attached to the nitrogen of the cyanoguanidine moiety are required for antiischemic activity. The mechanism of action of these compounds appear to involve opening of the KArP as structurally distinct KATP blockers abolish the cardioprotective effects of these compounds. Unlike the first generation compounds (e.g., cromakalim), the more selective KATP openers can be administered iv to observe antiischemic efficacy. The mechanism of antiischemic activity of KArP openers does not appear to involve the sarcolemmal KArP as their antiischemic activity is independent of action potential shortening. Progress at understanding the molecular mechanism of action of KArP openers and opportunities for future research are also discussed in this article.
Phytocompounds from the Medicinal and Dietary Plants: Multi-target Agents for Cervical Cancer Prevention and Therapy
Authors: Shoaib Shoaib , Islam Najmul , Yusuf Nabiha 
Published: March 2022

Abstract:Cervical cancer is the fourth leading cause of cancer death among women worldwide. Due to cervical cancer's high incidence and mortality, there is an unmet demand for effective diagnostic, therapeutic, and preventive agents. At present, the preferred treatment strategies for advanced metastatic cervical cancer include surgery, radiotherapy, and chemotherapy. However, cervical cancer is gradually developing resistance to chemotherapy, thereby reducing its efficacy. Over the last several decades, phytochemicals, a general term for compounds produced from plants, have gained attention for their role in preventing cervical cancer. This role in cervical cancer prevention has garnered attention on the medicinal properties of fruits and vegetables. Phytochemicals are currently being evaluated for their ability to block proteins involved in carcinogenesis and chemoresistance against cervical cancer. Chemoresistance to cancer drugs like cisplatin, doxorubicin, and 5-fluorouracil has become a significant limitation of drug-based chemotherapy. However, the combination of cisplatin with other phytochemicals has been identified as a promising alternative to subjugate cisplatin resistance. Phytochemicals are promising chemo-preventive and chemotherapeutic agents as they possess antioxidant, anti-inflammatory, and anti-proliferative potential against many cancers, including cervical cancer. Furthermore, the ability of the phytochemicals to modulate cellular signaling pathways through up and down regulation of various proteins has been claimed for their therapeutic potential. Phytochemicals also display a wide range of biological functions, including cell cycle arrest, apoptosis induction, inhibition of invasion, and migration in cervical cancer cells. Numerous studies have revealed the critical role of different signaling proteins and their signaling pathways in the pathogenesis of cervical cancer. Here, we review the ability of several dietary phytochemicals to alter carcinogenesis by modulating various molecular targets.
Antiviral Compounds Based on Natural Astragalus polysaccharides (APS): Research and Foresight in the Strategies for Combating SARS-CoV-2 (COVID-19)
Authors: Rafieian-Kopaei Mahmoud , Aleebrahim-Dehkordi Elahe , Heidari-Soureshjani Ehsan , Aryan Alisam , Ganjirad Zahra , Soveyzi Faezeh , Hoseinsalari Afsaneh , Derisi Mohamad Mehdi 
Published: March 2022

Abstract:
Today, finding natural polymers with desirable properties for use in various industries is one of the critical axes of research in the world. Polysaccharides are a group of natural polymers that have various applications in the pharmaceutical industry. The attachment of monosaccharides forms polysaccharides through glycosidic bonds that are widely found in various sources, including plants. Genus Astragalus belongs to the Fabaceae family. Plants belonging to this genus have different polysaccharides. Astragalus polysaccharides (APS) have attracted a great deal of attention among natural polymers because they are non-toxic, biodegradable, and biocompatible. Currently, APS have great drug potential for curing or treating various diseases. Due to the different biological activities of polysaccharides, including Astragalus, this study has investigated the chemical structure of APS, reporting on the antiviral and anti-inflammatory activities as well as stimulation of cytokine secretion by these polysaccharides. Also, in this study, the pharmaceutical approaches of APS compounds, as a natural, new and inexpensive source, have been discussed as suitable candidates for use in pharmaceutical formulations and preparation of new drugs to control COVID-19 infection
Synthesis and Anticancer Activities of Novel Bis-chalcones Incorporating
the 1,3-diphenyl-1H-pyrazole Moiety: In Silico and In Vitro Studies
Authors: Mohamed Magda F. , Sroor Farid M. , Elsayed Shahinda E. , Mahrous Karima F. , Mageed Lamiaa , Hanafy Mahmoud Khaled , Ibrahim Sherif A. , Elwahy Ahmed H. M. , Abdelhamid Ismail A. 
Published: March 2022

Abstract:
A new series of bis-chalcones 5-10 has been prepared by the condensation reaction of one
equivalent of bis(acetophenones) 3a-f with two equivalents of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde
4. The newly prepared compounds 5-10 have been fully characterized and evaluated as in vitro anticancer
agents against a panel of human cancer cell lines A431, A549, PC3, and a normal human skin
fibroblast BJ1.

Aims:
The current work is designed to explore the anti-cancer activity of novel bis-chalcones incorporating
a 1,3-diphenyl-1H-pyrazole moiety.

Background:
Chalcones represent one of the most important organic compounds that have been attracting
the interest of many researchers in drug discovery.

Objective:
The present study was carried out to explore anti-cancer activity of novel bis-chalcones incorporating
a 1,3-diphenyl-1H-pyrazole moiety as in vitro and in silico studies.

Materials and Methods:
We used the condensation reaction to prepare bis-chalcones incorporating 1,3-
diphenyl-1H-pyrazole moiety. The MTT Assay, Anti-cancer activity, Gene expression, DNA Fragmentation,
DNA Damage, and Molecular docking were investigated.

Results:
Compounds 5 and 9 were found to be the most promising compounds in the prepared series with
IC50 (50.3 and 50.1 μg/ml, respectively) against epidermoid cancer cell line A431 compared to doxorubicin
as a reference drug.

Conclusion:
All of these results showed that chalcones 5 and 9 have promising anti-cancer properties
without cytotoxic effect, which could make them a promising active component for further studies.
Novel S-Mercaptotriazolebenzothiazole-Based Derivatives as Antimicrobial
Agents: Design, Synthesis, and In Vitro Evaluation
Authors: Alqahtani Alaa M. , El-Din Asmaa G. Safi , Abdou Randa , Amin Ali H. , Arab Hany H. , Abdelazeem Ahmed H. 
Published: March 2022

Background:
The search for novel antimicrobial agents effective against the emerging resistant
pathogenic microorganisms to the currently used drugs is a substantial need. Herein, a novel series of
compounds bearing a benzothiazolotriazole scaffold was synthesized and evaluated as potential antimicrobial
agents against a panel of gram +ve, gram -ve bacteria, and fungi species.

Methods:
The new compounds were synthesized via hybridization between the benzothiazolotriazole
scaffold and thiadiazole ring or various substituted aromatic moieties using the tethering technique in
drug discovery.

Results:
The in vitro results revealed that these compounds have significant antifungal activity rather than
antibacterial potential due to their high similarity with tricyclazole. Compound 7b bearing bromo-phenyl
moiety was the most potent derivative with an MIC value of 8 μg/mL against Candida albicans and Penicillium
chrysogenum.

Conclusion:
Collectively, benzothiazolotriazole-based derivatives are good antifungal leads and should
be further actively pursued to expand treatment options for systemic and topical fungal infections.
Pyrazole based Furanone Hybrids as Novel Antimalarial: A Combined
Experimental, Pharmacological and Computational Study
Authors: Choudhary Deepika , Rani Isha , Monga Jyoti , Goyal Rajat , Husain Asif , Garg Prabha , Khokra Sukhbir Lal 
Published: March 2022

Background:
Malaria parasite strains are resistant to the therapeutic effect of prophylactics
medicines presently available. This resistance now poses a significant challenge to researchers
to beat malaria parasitic infections. Strategies such as investigating newer hybrid chemical
entities and specified drug targets may help us spot new efficient derivatives that bind to the
parasites in a more specific manner and inhibit their growth.

Objective:
To scientifically perform the experimental, pharmacological, and computational studies
of pyrazole-based furanone hybrids as novel antimalarial agents.

Methods:
A series of new furanone-based pyrazole derivatives were synthesized and investigated
as potential antimalarial agents by performing in vitro antimalarial activity. To get further optimization,
these synthesized derivatives were virtually screened based on ADME-T filters, and molecular
docking studies were also accomplished on the crystal structures of Plasmodium falciparum
lactate dehydrogenase (PfLDH). Furthermore, the in-silico prediction was supported by performing
an LDH assay.

Results:
The docking data suggested that the designed hybrid of furanone-pyrazole may act as
PfLDH inhibitors. It was found that the results of experimental in vitro antimalarial activity and in
silico analysis correlate well to each other to a good extent. The compounds (7d), (7g), and (8e)
were found to be the most potent derivatives with IC50 values of 1.968, 1.983, and 2.069 μg/ml, respectively.

Conclusion:
From the results, it may be concluded that compounds that are active in low doses
might be adopted as a lead compound for the development of more active antimalarial agents. The
synthesized compounds (7d), (7g), and (8e) exhibited good antimalarial activity with PfLDH inhibition.
The best compounds can be explored further in the future for designing the potent inhibitors
of PfLDH as new potent antimalarial agents.
Endoplasmic Reticulum Stress and Renin-Angiotensin System Crosstalk in
Endothelial Dysfunction
Authors: Gaikwad Anil Bhanudas , Sankrityayan Himanshu , Rao Pooja Dhileepkumar , Shelke Vishwadeep , Kulkarni Yogesh A. , Mulay Shrikant R. 
Published: March 2022

Background:
Vascular endothelial dysfunction (VED) significantly results in catastrophic car-diovascular diseases with multiple aetiologies. Variations in vasoactive peptides, including angiotensin II and endothelin 1, and metabolic perturbations like hyperglycaemia, altered insulin signalling, and homo-cysteine levels result in pathogenic signalling cascades, which ultimately lead to VED. Endoplasmic re-ticulum (ER) stress reduces nitric oxide availability, causes aberrant angiogenesis, and enhances oxidative stress pathways, consequently promoting endothelial dysfunction. Moreover, the renin-angiotensin sys-tem (RAS) has widely been acknowledged to impact angiogenesis, endothelial repair and inflammation. Interestingly, experimental studies at the preclinical level indicate a possible pathological link between the two pathways in the development of VED. Furthermore, pharmacological modulation of ER stress ameliorates angiotensin-II mediated VED as well as RAS intervention either through inhibition of the pressor arm or enhancement of the depressor arm of RAS, mitigating ER stress-induced endothelial dys-function and thus emphasizing a vital crosstalk.

Conclusion:
Deciphering the pathway overlap between RAS and ER stress may open potential therapeu-tic avenues to combat endothelial dysfunction and associated diseases. Several studies suggest that alter-ation in a component of RAS may induce ER stress or induction of ER stress may modulate the RAS components. In this review, we intend to elaborate on the crosstalk of ER stress and RAS in the patho-physiology of VED.
A Review on Structurally Diversified Synthesized Molecules as Monoacylglycerol Lipase Inhibitors and their Therapeutic uses
Authors: Kashyap Abhishek , Kumar Suresh , Dutt Rohit 
Published: March 2022

Abstract:
Monoacylglycerol is a metabolic key serine hydrolase engaged in the regulation of the
signalling network system of endocannabinoids, which is associated with various physiological
processes like pain, inflammation, feeding cognition, and neurodegenerative diseases like Alzheimer’s
and Parkinson’s disease. The monoacylglycerol was also found to act as a regulator and
the free fatty acid provider in the proliferation of cancer cells as well as numerous aggressive tumours
such as colorectal cancer, neuroblastoma, and nasopharyngeal carcinoma. It also played an
important role in increasing the concentration of specific lipids derived from free fatty acids like
phosphatidic acid, lysophosphatidic acid, sphingosine-1-phosphate, and prostaglandin E2. These
signalling lipids are associated with cell proliferation, survival, tumour cell migration, contribution
to tumour development, maturation, and metastases. In this study, we present a review on structurally
diverse MAGL inhibitors, their development, and their evaluation for different pharmacological
activities.
Impact of the COVID-19 Pandemic on Dermatology Practice Worldwide: Results of a Survey Promoted by the International Dermoscopy Society
Authors: Conforti Claudio 
Published: March 2022

Background
The International Dermoscopy Society (IDS) conducted an online survey to investigate the impact of the COVID-19 outbreak on the daily practice of dermatologists working with patients with skin cancer, to collect data regarding the frequency of skin manifestations noticed by the members, and to obtain information about the use of teledermatology during the pandemic.

Objective
The aims of this study are to identify changes within dermatology departments during lockdowns, to evaluate the use of teledermatology during the COVID-19 pandemic, and to find the most frequent cutaneous manifestations associated with COVID-19.

Methods
All IDS members (approximately 160,000 members) were asked to fill in a questionnaire sent by email. The questionnaire was available in English and was anonymous, with a compiling time of less than 5 minutes. The survey was open for 30 days (from April 24, 2020, to May 24, 2020) and it could only be filled out once.

Results
Overall, 678 dermatologists responded to the questionnaire; of these, 334 members stated that there had been a reduction of more than 75% in daily work activity during the pandemic, 265 dermatologists worked fewer days per week, and 118 experienced telemedicine for the first time. Acrodermatitis was the most frequently observed skin manifestation (n=80), followed by urticarial rash (n=69), morbilliform rash (n=53), and purpuric manifestation (n=40). Regarding the role of teledermatology, 565 dermatologists reported an increased number of teleconsultations, and the number of melanomas diagnosed during the pandemic was practically 0 for 385 (56.8%) respondents.

Conclusions
This survey highlights that the outbreak had a negative impact on most dermatology services, with a significant reduction in consultation time spent for patients with chronic conditions, and an increased risk of missed melanoma and nonmelanoma skin cancer diagnosis. Moreover, our study confirms earlier findings of a wide range of skin manifestations associated with COVID-19.

Conflicts of Interest
None declared.
Confocal Microscopy and its Role in Teledermatology: Diagnosis of Basal Cell Carcinoma in a Clinical Setting
Authors: Garfinkel Jason , Chandler C , Rubinstein G , Jain Manu 
Published: March 2022

Background
Reflectance confocal microscopy (RCM) is a noninvasive tool that is used to diagnose skin cancers. However, RCM requires an expert consultation, which is often performed via store-and-forward (SAF) teledermatology. Unfortunately, SAF does not mimic bedside diagnosis, nor permits interaction between the remote expert reader, physician, and patient. Recently, a live interactive method (LIM)–tele-RCM approach was shown to diagnose basal cell carcinoma (BCC) from a remote location, demonstrating advantages over SAF by providing a bedside diagnosis during consultation.

Objective
The aim of this study is to validate the LIM-tele-RCM approach to diagnose BCC in a real-world setting.

Methods
In this pilot study, 4 patients with 6 clinically suspicious BCC lesions were enrolled and imaged with RCM at a Los Angeles dermatology clinic. A Health Insurance Portability and Accountability Act–compliant teleconferencing application was used to livestream RCM images to an expert RCM reader in New York. The expert reader had remote control of the software, direct audio communication with the clinic, and the patient’s clinical history with dermoscopy. During imaging, RCM features were noted, and a diagnosis was made at the bedside. After imaging, patients completed a short questionnaire (on a 5-point scale, with 5 being the highest score) about satisfaction, comfort, and communication during the session.

Results
RCM diagnosed 4/6 (67%) lesions correctly as BCC and 2/6 (33%) were false-positive diagnoses. The true-positive lesions had “tumor islands with palisading and clefting” and were directly managed with Mohs surgery. The false-positive lesions had “dark silhouettes” (a common false-positive feature for BCC) and underwent a shave biopsy for confirmation. The entire session ranged from 15 to 20 minutes (an average of 17.7 minutes), comparable to the reported RCM procedure time. On the questionnaire, all patients responded with the highest rating (5/5) for each question.

Conclusions
LIM-tele-RCM demonstrates potential advantages over the SAF method, enabling bedside diagnosis with similar diagnostic accuracy as reported in the literature and proper management. Additionally, the remote reader had access to patients’ clinical backgrounds and could engage with patients. It may also be useful for training novice RCM users and beneficial in settings where remote diagnostics are desired, such as during the COVID-19 pandemic. However, technical challenges such as image quality degradation during video streaming, poor internet bandwidth, and end user latency may impact diagnosis. Larger, multicenter studies are needed to assess the accuracy of LIM-tele-RCM for the diagnosis of BCC and other neoplastic and inflammatory lesions, and to quantify technical limitations.

Acknowledgments
This work was funded by the National Cancer Institute Cancer Center (Grant P30 CA008748).

Conflicts of Interest
None declared.
Confocal Microscopy and its Role in Teledermatology: Diagnosis of Basal Cell Carcinoma in a Clinical Setting (Preprint)
Authors: Garfinkel Jason , Chandler C , Rubinstein G , Jain Manu 
Published: March 2022

BACKGROUND

Reflectance confocal microscopy (RCM) is a noninvasive tool that is used to diagnose skin cancers. However, RCM requires an expert consultation, which is often performed via store-and-forward (SAF) teledermatology. Unfortunately, SAF does not mimic bedside diagnosis, nor permits interaction between the remote expert reader, physician, and patient. Recently, a live interactive method (LIM)–tele-RCM approach was shown to diagnose basal cell carcinoma (BCC) from a remote location, demonstrating advantages over SAF by providing a bedside diagnosis during consultation.

OBJECTIVE

The aim of this study is to validate the LIM-tele-RCM approach to diagnose BCC in a real-world setting.

METHODS

In this pilot study, 4 patients with 6 clinically suspicious BCC lesions were enrolled and imaged with RCM at a Los Angeles dermatology clinic. A Health Insurance Portability and Accountability Act–compliant teleconferencing application was used to livestream RCM images to an expert RCM reader in New York. The expert reader had remote control of the software, direct audio communication with the clinic, and the patient’s clinical history with dermoscopy. During imaging, RCM features were noted, and a diagnosis was made at the bedside. After imaging, patients completed a short questionnaire (on a 5-point scale, with 5 being the highest score) about satisfaction, comfort, and communication during the session.

RESULTS

RCM diagnosed 4/6 (67%) lesions correctly as BCC and 2/6 (33%) were false-positive diagnoses. The true-positive lesions had “tumor islands with palisading and clefting” and were directly managed with Mohs surgery. The false-positive lesions had “dark silhouettes” (a common false-positive feature for BCC) and underwent a shave biopsy for confirmation. The entire session ranged from 15 to 20 minutes (an average of 17.7 minutes), comparable to the reported RCM procedure time. On the questionnaire, all patients responded with the highest rating (5/5) for each question.

CONCLUSIONS

LIM-tele-RCM demonstrates potential advantages over the SAF method, enabling bedside diagnosis with similar diagnostic accuracy as reported in the literature and proper management. Additionally, the remote reader had access to patients’ clinical backgrounds and could engage with patients. It may also be useful for training novice RCM users and beneficial in settings where remote diagnostics are desired, such as during the COVID-19 pandemic. However, technical challenges such as image quality degradation during video streaming, poor internet bandwidth, and end user latency may impact diagnosis. Larger, multicenter studies are needed to assess the accuracy of LIM-tele-RCM for the diagnosis of BCC and other neoplastic and inflammatory lesions, and to quantify technical limitations.