bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Cannabis and its Constituents in Disease Management:
Insights from Clinical Studies
Authors: Vimal Divya , D’Souza Leonard Clinton , Rai Vipin , Lal Samridhi , Sharma Anurag , Gupta Subash Chandra 
Published: May 2022

Abstract:
There is a long history of informal use of Cannabis sativa (commonly called cannabis) for many purposes, including treating various ailments worldwide. However, the legalization of cannabis in multiple countries, specifically for medical purposes, has grabbed the researchers' attention to discover the scientific evidence of cannabis’s beneficial effects. Among over 500 identified compounds (cannabinoids), Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are two major active cannabinoids derived from cannabis. Cannabinoids exert their effects through cannabinoid receptors (CB1R and CB2R). In the recent past, clinical trials have shown the efficacy of cannabis and cannabinoids for various human ailments such as cancer, neurological disorders, inflammatory bowel disease, chronic pain, and metabolic disorders. The commonly used constituents and derivatives of cannabis include CBD, THC, THCV, dronabinol, nabilone, and nabiximol. The cannabis constituents have also been used in combination with other agents such as megestrol acetate in some clinical trials. The common routes for the administration of cannabis are oral, sublingual, or topical. Cannabis has also been consumed through smoking, inhalation, or with food and tea. As high as 572 patients and as low as nine patients have participated in a single clinical trial. Cannabis is legalized in some countries with restrictions, such as Belize, Canada, Colombia, Costa Rica, The Czech Republic, Jamaica, Netherlands, South Africa, Spain, and Uruguay. This article provides a compilation of published studies focusing on clinal trials on the therapeutic effects of cannabis. The adverse effects of cannabis and its constituents are also discussed.
Ruscogenin Alleviates Deep Venous Thrombosis and Pulmonary Embolism Induced
by Inferior Vena Cava Stenosis Inhibiting MEK/ERK/Egr-1/TF Signaling Pathway
in Mice
Authors: Dai Yujie , Zhou Qianliu , Liu Yuankai , Chen Xiaojun , Li Fang , Yu Boyang , Zhang Yuanyuan , Kou Junping 
Published: May 2022

Background:
Ruscogenin (RUS) has anti-inflammatory and antithrombotic effects, while its potential
effects on deep venous thrombosis (DVT) and pulmonary embolism (PE) remain unclear.

Objective:
We aimed to elucidate the effects of RUS on DVT and PE induced by the inferior vena cava stenosis
(IVCS) model and investigate the underlying mechanism.

Methods:
Male C57/BL6 mice were used to explore whether IVCS model could be complicated with deep
venous thrombosis and pulmonary embolism. Then, effects of RUS on DVT and PE related inflammatory
factors and coagulation were examined using H&E staining, ELISA, and real-time PCR. Western blot analysis
was used to examine the effects of RUS on MEK/ERK/Egr-1/TF signaling pathway in PE.

Results:
IVCS model induced DVT and complied with PE 48 h after surgery. Administration of RUS (0.01,
0.1, 1 mg/kg) inhibited DVT, decreased biomarker D-Dimer, cardiac troponin I, N-Terminal probrain natriuretic
peptide in plasma to ameliorate PE induced by IVCS model. Meanwhile, RUS reduced tissue factor and
fibrinogen content of lung tissue, inhibited P-selectin and C-reactive protein activity in plasma, and suppressed
the expressions of interleukin-6 and interleukin-1β in mice. Furthermore, RUS suppressed the phosphorylation
of ERK1/2 and MEK1/2, decreasing the expressions of Egr-1 and TF in the lung.

Conclusion:
IVCS model contributed to the development of DVT and PE in mice and was associated with
increased inflammation. RUS showed therapeutic effects by inhibiting inflammation as well as suppressing the
activation of MEK/ERK/Egr-1/TF signaling pathway.
Development of Simple Dissolution Methods for Felodipine and Combined Amlodipine
Besylate-Indapamide Extended Release Tablets without Stationary (Felodipine)
Basket
Authors: Javed Arslan , Kanwal Ummarah , Gilani Syed Ahmad Nazir , Akhtar Farhan , Shamim Rahat , Abbas Nasir , Bukhari Nadeem Irfan 
Published: May 2022

Background:
The dissolution method for certain drugs needs specialized conditions. Dissolution
testing for felodipine extended release (ER) tablets (Plendil® 5 mg) and amlodipine-indapamide fixed dose
(Natrilam®, 5/1.5 mg) ER tablets requires the use of a stationary (felodipine) basket in USP Apparatus II.

Objective:
The study aimed to develop simple methods for Plendil® and Natrilam® without the use of a felodipine
basket.

Method:
The dissolution profiles obtained from different media and paddle speeds were used to compute miscellaneous
dissolution parameters and were compared to those obtained from standard (existing) methods using
a felodipine basket.

Results:
The f1, f2, and bootstrap f2 (5th % percentile) values for Plendil® 2.47, 88.17, and 54.62, respectively,
and all other dissolution factors revealed similarity between standard and the selected test method with 1%
Tween 20 at 50 rpm. For Natrilam®, f1 and f2 and bootstrap f2 5.13, 72.92, and 62.67, respectively, and all other
dissolution parameters showed similarity of the standard and selected test method using 0.1N HCl media
having 0.38 gm/L EDTA with a sinker at 100 rpm. Release of products assumed zero-order and Weibull model,
respectively.

Conclusion:
Test dissolution methods for Plendil® and Natrilam® tablets produced equivalent dissolution profiles
compared to their respective standard methods with stationary basket USP Apparatus II.
Liquid Chromatography High-Resolution Mass Spectrometry in Forensic
Toxicology: What are the Specifics of Method Development, Validation and Quality
Assurance for Comprehensive Screening Approaches?
Authors: Wille Sarah M.R. , Desharnais Brigitte , Pichini Simona , Trana Annagiulia Di , Busardò Francesco Paolo , Wissenbach Dirk K. , Peters Frank Theodor 
Published: May 2022

Abstract:
The use of High Resolution Mass Spectrometry (HRMS) has increased over the past decade in clinical and forensic toxicology, especially for comprehensive screening approaches. Despite this, few guidelines of this field have specifically addressed HRMS issues concerning compound identification, validation, measurement uncertainty and quality assurance. To fully implement this technique, certainly in an era in which the quality demands for laboratories are ever increasing due to various norms (e.g. the International Organization for Standardization’s ISO 17025), these specific issues need to be addressed. This manuscript reviews 26 HRMS-based methods for qualitative systematic toxicological analysis (STA) published between 2011 and 2021. Key analytical data such as samples matrices, analytical platforms, numbers of analytes and employed mass spectral reference databases/libraries as well as the studied validation parameters are summarized and discussed. The article further includes a critical review of targeted and untargeted data acquisition approaches, available HRMS reference databases and libraries as well as current guidelines for HRMS data interpretation with a particular focus on identification criteria. Moreover, it provides an overview on current recommendations for the validation and determination measurement uncertainty of qualitative methods. Finally, the article aims to put forward suggestions for method development, compound identification, validation experiments to be performed, and adequate determination of measurement uncertainty for this type of wide-range qualitative HRMS-based methods.
Investigating the Metabolic Mechanisms of Butaselen, An Ebselen Analog
Authors: Tian Qianqian , Jiang Jinfang , Yin Hanwei , Zhang Yifan , Li Yilin , Wu Ping , Peng Chao , Wang Zhijie , Zhou Jialan , Zeng Huihui , Zhong Dafang 
Published: May 2022

Background:
Butaselen is an ebselen analog that is under clinical trials for treating hepatic and pulmonary
fibrosis. Our previous studies showed that butaselen is mainly present in human plasma in the form of M2, a
free Se-methylated metabolite.

Objective:
This study aimed to investigate the metabolic mechanisms of butaselen.

Methods and Results:
Butaselen was incubated with human plasma. Butaselen immediately disappeared, and the
butaselen-HSA (human serum albumin) adduct was detected by HPLC-HRMS, showing that butaselen covalently
binds to HSA. The butaselen-HSA adduct was precipitated using acetonitrile and then incubated with PBS, Cys, and
GSH for 1 hour. The product was M1, a reduced form of butaselen. The results indicated that HSA, Cys, and GSH
can reduce the butaselen-HSA covalent bond. The binding site for butaselen could be the cysteine-34 residue of HSA
through pronase and trypsin hydrolysis. Incubating butaselen with cysteine, butaselen-Cys, butaselen-2Cys, and M1
were generated, indicating the covalent binding and reduction of butaselen by cysteine. We incubated liver microsomes
and cytosol with butaselen, 6.22 and 246 nM M2 were generated, respectively. The results demonstrated that
cytosolic enzymes are mainly involved in M2 production. The amount of M2 in the liver cytosol decreased from 246
nM to 2.21 nM when 10 mM m-anisic acid (a specific TPMT enzyme inhibitor) was added, showing that TPMT is
responsible for M2 formation.

Conclusion:
Butaselen was covalently bound to HSA, and the binding site was the cysteine-34 residue of HSA. The
butaselen-HSA adduct was reduced by free thiol compounds to generate M1. M1 was further metabolized to M2 by
cytosolic TPMT. This study provides a basis for studying the pharmacokinetics of selenium-containing drugs.
Nucleic Acid Nanotechnology: Trends, Opportunities and Challenges
Authors: Singh Raghvendra Pratap , Manchanda Geetanjali , Dubey R.C. , Srivastava Atul K. , Yang Ying-Jie , Kumar Ajay , Yerpude Sachin T. , Rai Alok R. 
Published: May 2022

Abstract:
Nucleic acids (DNA and RNA) hold great potential for the advancement of future medicine but suffer from unsatisfactory clinical success due to the challenges accompanied with their delivery. Nucleic acid mediated nanomaterials have riveted the researchers from past two decades and exhilarating tasks have prevailed. Nucleic acid nanotechnology offers unique control over the shape, size, time, mechanistic, and anisotropy. It can transfect numerous types of tissues and cells without any toxic effect, minimize the induced immune response, and penetrate most of the biological barriers and hence it reveals itself as a versatile tool for multidisciplinary research field and for various therapeutic purposes. Nucleic acid combines with other nanoscale objects also by altering the chemical functional groups and reproducing the varied array of nanomaterials. Interestingly, nucleic acid derived nanomaterials are characterized easily at atomic level accuracy. However, this advent nanoscience has vital issues which must be addressed, such as the high cost of nucleic acids, their self-assembly nature, etc. Hence, the aim of this review is to highlights the systematic advances and methodology of nucleic acid mediated synthesis of nanomaterials and their therapeutic applications.
Number of Detected Proteins as the Function of the Sensitivity of Proteomic
Technology in Human Liver Cells
Authors: Archakov Alexander , Vavilov Nikita , Ilgisonis Ekaterina , Lisitsa Andrey , Ponomarenko Elena , Farafonova Tatiana , Tikhonova Olga , Zgoda Victor 
Published: May 2022

Aims:
The main goal of the Russian part of C-HPP is to detect and functionally annotate
missing proteins (PE2-PE4) encoded by human chromosome 18. To achieve this goal, it is necessary to
use the most sensitive methods of analysis.

Background:
However, identifying such proteins in a complex biological mixture using mass spectrometry
(MS)-based methods is difficult due to the insufficient sensitivity of proteomic analysis methods.
A possible solution to the problem is the pre-fractionation of a complex biological sample at the
sample preparation stage.

Objective:
This study aims to measure the detection limit of SRM SIS analysis using a standard set of
UPS1 proteins and find a way to enhance the sensitivity of the analysis and to, detect proteins encoded
by the human chromosome 18 in liver tissue samples, and compare the data with transcriptomic analysis
of the same samples.

Methods:
Mass spectrometry, data-dependent acquisition, selected reaction monitoring, highperformance
liquid chromatography, data-dependent acquisition in combination with pre-fractionation
by alkaline reversed-phase chromatography, selected reaction monitoring in combination with prefractionation
by alkaline reversed-phase chromatography methods were used in this study.

Results:
The results revealed that 100% of UPS1 proteins in a mixture could only be identified at a
concentration of at least 10-9 М. The decrease in concentration leads to protein losses associated with
technology sensitivity, and no UPS1 protein is detected at a concentration of 10-13 М. Therefore, the
two-dimensional fractionation of samples was applied to improve sensitivity. The human liver tissue
was examined by selected reaction monitoring and shotgun methods of MS analysis using onedimensional
and two-dimensional fractionation to identify the proteins encoded by human chromosome
18. A total of 134 proteins were identified. The overlap between proteomic and transcriptomic data in
human liver tissue was ~50%.

Conclusion:
The sample concentration technique is well suited for a standard UPS1 system that is not
contaminated with a complex biological sample. However, it is not suitable for use with a complex biological
protein mixture. Thus, it is necessary to develop more sophisticated fractionation systems for the
detection of all low-copy proteins. This weak convergence is due to the low sensitivity of proteomic
technology compared to transcriptomic approaches. Also, total mRNA was used to perform RNA-seq
analysis, but not all detected mRNA molecules could be translated into proteins. This introduces additional
uncertainty in the data; in the future, we plan to study only translated mRNA molecules-the translatome.
Data is available via ProteomeXchange with identifier PXD026997.
Taming the Devil: Antimicrobial Peptides for Safer TB Therapeutics
Authors: Verma Rahul Kumar , Jadhav Krishna , Singh Raghuraj , Ray Eupa , Singh Amit Kumar 
Published: May 2022

Abstract:Tuberculosis (TB) is a highly contagious infection with extensive mortality and morbidity. The rise of TB-superbugs (drug-resistant strains) with the increase of their resistance to conventional antibiotics has prompted a further search for new anti-mycobacterial agents. It is difficult to breach the barriers around TB bacteria, including mycolic cell wall, granuloma, biofilm and mucus, by conventional antibiotics in a short span of time. Hence, there is an essential need for molecules with an unconventional mode of action and structure that can efficiently break the barriers around mycobacterium. Antimicrobial peptides (AMP) are essential components of innate immunity having cationic and amphipathic characteristics. Lines of evidence show that AMPs have good myco-bactericidal and antibiofilm activity against normal as well as antibiotic-resistant TB bacteria. These peptides have shown direct killing of bacteria by membrane lysis and indirect killing by activation of innate immune response in host cells by interacting with the component of the bacterial membrane and intracellular targets through diverse mechanisms. Despite a good anti-mycobacterial activity, some undesirable characteristics are also associated with AMP, including hemolysis, cytotoxicity, susceptibility to proteolysis and poor pharmacokinetic profile, and hence only a few clinical studies have been conducted with these biomolecules. The design of new combinatorial therapies, including AMPs and particulate drug delivery systems, could be new potential alternatives to conventional antibiotics to fight MDR- and XDRTB. This review outlined the array of AMP roles in TB therapy, possible mechanisms of actions, activities, and current advances in pragmatic strategies to improve challenges accompanying the delivery of AMP for tuberculosis therapeutics.
Antidiabetic Potential of Selected Ethnomedicines Utilized for the Management of Diabetes Mellitus in Trinidad and Tobago: A Review
Authors: Powder-George Yomica L. , Deonarine Rajiv D. 
Published: May 2022

Background:
Diabetes is a chronic metabolic disorder with a high global prevalence
and one of the highest morbidity and mortality rates. Despite developments in synthetic medicine,
the associated serious side effects with current antidiabetic drugs indicate an urgent need for novel
effective treatments. Traditional medicinal plants offer great potential in the treatment of many diseases
due to their bioactive phytochemicals and are a useful resource for developing safe and effective
hypoglycemic agents.

Methods:
The present review collates the most frequently used ethnomedicines for the management
of diabetes mellitus in Trinidad and Tobago. Further, it provides scientific validation of the
claimed antidiabetic effects of four selected ethnomedicines: Antigonon leptopus, Gomphrena globosa,
Laportea aestuans and Stachytarpheta jamaicensis. A comprehensive literature search was
conducted using various electronic scientific databases and search engines. Information was collected
on the phytochemical and pharmacological aspects of these selected species to illustrate the
antidiabetic activity and potential applications of these plants.

Conclusion:
The findings of the numerous in vitro and in vivo experiments from previously published
literature indicate the four candidate plants as promising sources of antidiabetic lead compounds
and provide useful information to stimulate extensive studies. Further investigations on the
isolation, identification and clinical evaluation of the pharmacologically active constituents from
these plants can lead to the discovery of new and effective antidiabetic agents.
Telemedicine for Diabetes Mellitus Management in Older Adults: A Systematic
Review
Authors: Tristão Luca Schiliró , Tavares Guilherme , Tustumi Francisco , Bernardo Wanderley Marques , Duarte Márcio Luis , Peccin Maria Stella , dos Santos Lucas Ribeiro 
Published: May 2022

Background:
Diabetes mellitus affects almost 20% of the world’s population between
65 and 99 years old. The care for this disease urges a complex, multidisciplinary, and stepwise approach.
Telemedicine has been evaluated, and clinical trials as well as systematic reviews have
been performed, and most have shown the benefits of its use in DM management. However, as the
prevalence of diabetes mellitus increases, as well as the population ages, considerations regarding
access and compliance of older patients to such technologies arise.

Objective:
The study aimed to determine the efficacy of telemedicine medical consultations in
comparison to standard face-to-face consultations.

Methods:
A systematic literature search to identify trials investigating the effect of telemedicine
medical consultations in clinical-laboratory aspects of DM management was conducted. The search
was carried out in electronic databases: Medline, EMBASE, LILACS, ClinicalTrials.gov, and the
CENTRAL Cochrane. Two authors independently assessed the included studies using the proper
bias assessment tool for each study design.

Results:
In agreement with the eligibility criteria, three studies were included. In terms of the main
outcome, HbA1c, only one out of three articles showed a significant difference between the
groups, favoring patients in the telemedicine group. With respect to blood pressure, Sood A reported
that the usual care group exhibited a greater improvement in systolic blood pressure with statistical
differences. All other results displayed no significant statistical difference between the groups.
Also, no statistical difference was found in most of the lipid profile results.

Conclusion:
Our review shows that teleconsultations do not provide a clear benefit to elderly people
with diabetes, but they may be non-inferior.
Safety and Performance of Continuous Glucose Monitoring: An Overview
Authors: Venkatesan Vijayalakshmi , Singh Himadri 
Published: May 2022

Abstract:
Diabetes (Type 1 and Type 2) is the most burdensome condition for the healthcare systems
worldwide. Continuous glucose monitoring (CGM) is a powerful tool in the management of
diabetes that has helped patients with diabetes to achieve better glycemic control as compared to
traditional systems. It helps reduce the frequency as well as the severity of hypoglycemia. Continuous
glucose monitoring technology is an integral part of the ‘artificial pancreas’. This review provides
an overview of CGM technology and its applications.
Transition Metal Coordination Complexes of Flavonoids: A Class of Better Pharmacological
Active Molecules to Develop New Drugs
Authors: Selvaraj Stalin , Jayaprakash Sushmitha , Ramesh Sruthi , Karthikeyan Aishwarya , Murugappan Sivasubramanian , Sidharthan Priyadharshini 
Published: May 2022

Abstract:
Flavonoid metal ion complexes are one of the classes of biologically active molecules with immense pharmacological
potential, including antioxidant, antidiabetic, antimicrobial, and anticancer activity, to name a few. The
effectiveness of this complexion depends on the state and nature of the transition metal ions and on the position to
which the metal ion coordinates with their corresponding parent flavonoid. The metal coordination of flavonoids also
improves the biological activities to a maximum extent compared to the parent compound. This may be attributed to
many factors such as metal ions, coordination sites, structural configuration, and stability of the complexes. On the
other hand, some of the metal ion complexes reduce the biological efficiency of the corresponding parent flavonoids,
which can be due to the shift from antioxidant to pro-oxidant nature as well as the stability of the complexes both in in
vitro and in vivo conditions. However, the literature on the stability of flavonoid metal ion complexes in in vivo conditions
is very scanty. Therefore, this review summarizes and critically addresses all these parameters a favor together in
a single slot that favours for the researchers to put forward to understand the mode and detailed molecular mechanism
of flavonoid metals complexes compared with their corresponding parent flavonoids.