bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in Anti-inflammatory Activity, Mechanism and Therapeutic
Application of Ursolic Acid
Authors: Meng Qingguo , Luan Mingzhu , Wang Huiyun , Wang Jiazhen , Zhang Xiaofan , Zhao Fenglan , Liu Zongliang 
Published: September 2021

:
In vivo and in vitro studies reveal that Ursolic Acid (UA) is able to counteract endogenous
and exogenous inflammatory stimuli and has favorable anti-inflammatory effects. The antiinflammatory
mechanisms mainly include decreasing the release of histamine in mast cells, suppressing
the activities of lipoxygenase, cyclooxygenase and phospholipase, and reducing the production of
nitric oxide and reactive oxygen species, blocking the activation of the signal pathway, downregulating
the expression of inflammatory factors, and inhibiting the activities of elastase and complement.
These mechanisms can open up new avenues for the scientific community to develop or improve
novel therapeutic approaches to tackle inflammatory diseases, such as arthritis, atherosclerosis,
neuroinflammation, liver diseases, kidney diseases, diabetes, dermatitis, bowel diseases, cancer. The
anti-inflammatory activity, the anti-inflammatory mechanism of ursolic acid and its therapeutic applications
are reviewed in this paper.
Advances in Biocatalytic Synthesis, Pharmacological Activities, Pharmaceutical
Preparation and Metabolism of Ginsenoside Rh2
Authors: Chai Xiaoyun , Meng Qingguo , Liu Li , Wang Huiyun , Jiang Sheng , Zhao Fenglan 
Published: September 2021

:
Ginsenoside Rh2 (3β-O-Glc-protopanaxadiol), a trace but characteristic pharmacological
component of red ginseng, exhibited versatile pharmacological activities, such as antitumor effects,
improved cardiac function and fibrosis, anti-inflammatory effects, antibiosis and excellent medicinal
potential. In recent years, increased research has been performed on the biocatalytic synthesis of ginsenoside
Rh2. In this paper, advances in the biocatalytic synthesis, pharmacological activities, pharmaceutical
preparation and metabolism of ginsenoside Rh2 are reviewed.
Acanthospermum hispidum DC: An Updated Review on Phytochemistry and Biological Activities
Authors: dos Santos Ewelyn Cintya Felipe , Machado Janaina Carla Barbosa , Ferreira Magda Rhayanny Assunção , Soares Luiz Alberto Lira 
Published: September 2021

Background:Acanthospermum hispidum DC is a medicinal plant present in America, Africa, Australia, India, Hawaii, and Brazil. In Brazil, the species is used in the treatment of gastrointestinal, respiratory disorders and has expectorant action. In the literature, there are studies on the chemical composition of the species, with reports of the presence of alkaloids, flavonoids, hydrolyzable tannins, terpenes, and steroids. In addition, several studies have reported in vitro and in vivo studies that prove the biological properties of extracts and compounds isolated from different organs of the A. hispidum plant, including hepatoprotectors, antioxidants, antimicrobials and antiparasitic.Objective:The objective of this review is to update the knowledge about the phytochemical, pharmacological and toxicity aspects of A. hispidum, and to contribute to the recognition of the species and direct new studies.Methods:An extensive bibliographic search was conducted in different scientific databases.Results:The presence of different chemical constituents in A. hispidum has been identified, among these constituents are flavonoids, tannins, terpenes, and steroids. Additionally, antimicrobial and antiparasitic activities were mainly attributed to the species, and other activities not previously described were presented, such as anticholinesterase, antioxidant, hepatoprotective, and hypoglycemic, all based on results of in vitro and in vivo studies. Finally, no reports of toxic effects were found in the in vitro and in vivo tests. After analyzing the articles, it was evidenced that other experiments with different models using animals are essential to evaluate the possible mechanisms of action of the extracts and compounds isolated of A. hispidum.Conclusion:Therefore, this review may contribute to the recognition of the importance of A. hispidum and its potential as a medicinal plant and may also guide the conduct of future research regarding the constituents, biological activities, and toxicity of the species.
Current Perspective of ATP Synthase Inhibitors in the Management of the Tuberculosis
Authors: Divita K. M. , Khatik Gopal L. 
Published: September 2021

Introduction:
Tuberculosis is a life-threatening disease, and the drugs discovered during the era of 1950 and 1970 are found inefficient due to emergent MDR and XDR-TB. Tuberculosis is difficult to treat due to the development of antibiotic resistance. ATP synthase is consisting of two units, F1 and F0 units. These are present in the cytoplasm and membrane of mitochondria, respectively. F1 unit comprises of a, b, and c subunit while F0 subunit has α, β, γ, δ, ε subunits. Bedaquiline is the first approved ATP synthase inhibitor in 2012 by USFDA.

Methods:
Recent literature from 2005-2020 were collected using Pubmed with the keywords ATP synthase inhibitor, bedaquiline derivatives, tuberculosis. The work describing detailed analyses of bedaquiline (BDQ) was included in the current work, and others were excluded.

Results:
ATP production occurs via the ATP synthase enzyme, leading to the growth and multiplication of mycobacteria. BDQ inhibits the mycobacterium ATP synthase enzyme, a heteropolymeric complex consisting of two subunits, but it does not interfere with mammalian ATP synthase. Bedaquiline (BDQ) has become a drug of choice to treat MDR-TB and help to reduce the treatment span. Recently observed triple mutation as wtLeu59A → mtVal59A; wtIle66A→ mtMet66A and wtGlu61B → mtAsp61B of ATP synthase led to decrease BDQ binding affinity; thus, researchers are putting efforts for its newer derivative discovery.

Conclusion:
ATP synthase inhibitor could be an alternative approach for better treatment of tuberculosis. Herein we discussed the recent advancements in the development of newer analogues of BDQ with its future perspectives.
Natural and Synthetic Naphthoquinones as Potential Anti-Infective Agents
Authors: Ortiz-Pérez Eyra , Rivera Gildardo , Salas Cristian O. , Zarate-Ramos Juan J. , Trofymchuk Oleksandra S. , Hernandez-Soberanis Lucio , Perales-Flores Juanita D. , Vázquez Karina 
Published: September 2021

Background:
Naphthoquinones are a class of aromatic compounds relevant for their
chemical characteristics, structural properties, and biological activity. These compounds are found in
nature with a wide range of effects, highlighting their antibacterial, antifungal, and antiprotozoal
properties. Additionally, naphthoquinones are used as a scaffold to obtain new derivatives with pharmacological
potential, mainly compounds against parasitic diseases.

Objective:
The purpose of this work was to carry out a comprehensive review of naphthoquinones
and their derivatives obtained from both natural and synthetic sources, also, to analyze their biological
activity against Leishmania spp. (Leishmaniasis), Trypanosoma cruzi (Chagas disease), Plasmodium
falciparum (Malaria), Toxoplasma gondii (Toxoplasmosis), and Toxocara canis (Toxocariasis).
All of these agents are responsible for relevant diseases worldwide.

Results :
Natural naphthoquinones, such as plumbagin, diospyrin, burmanin, lapachol, lawsone and
psychorubrin, show an antiprotozoal activity similar or enhanced antiprotozoal activity to reference
drugs. Some naphthoquinones obtained by synthesis or semi-synthesis showed better biological activity
or less toxic effects than natural compounds.

Conclusion:
In this review, natural and synthetic naphthoquinones showed antiparasitic activity, in
most cases, with improved results than current drugs currently used in clinical trials. A modification
of their structure with different functional groups can enhance their biological effects, improve solubility,
and reduce undesirable side effects. Therefore, naphthoquinones are important molecules in the
development of new chemotherapeutic agents against parasitic diseases.
Fruits for Seizures? A Systematic Review on the Potential Anti-Convulsant Effects of Fruits and their Phytochemicals
Authors: Shaikh Mohd. Farooq , Siang Lee Hsien , Arulsamy Alina , Yoon Yeong Keng 
Published: September 2021

:Epilepsy is a devastating neurological disorder. Current anti-convulsant drugs are only effective in about 70% of patients, while the rest remain drug-resistant. Thus, alternative methods have been explored to control seizures in these drug-resistant patients. One such method may be through the utilization of fruit phytochemicals. These phytochemicals have been reported to have beneficial properties such as anti-convulsant, anti-oxidant, and anti-inflammatory activities. However, some fruits may also elicit harmful effects. This review aims to summarize and elucidate the anti- or pro-convulsant effects of fruits used in relation to seizures in hopes of providing a good therapeutic reference to epileptic patients and their carers. Three databases, SCOPUS, ScienceDirect, and PubMed, were utilized for the literature search. Based on the PRISMA guidelines, a total of 40 articles were selected for critical appraisal in this review. Overall, the extracts and phytochemicals of fruits managed to effectively reduce seizure activities in various preclinical seizure models, acting mainly through the activation of the inhibitory neurotransmission and blocking the excitatory neurotransmission. Only star fruit has been identified as a pro-convulsant fruit due to its caramboxin and oxalate compounds. Future studies should focus more on utilizing these fruits as possible treatment strategies for epilepsy.
Lipid Behavior in Metabolic Syndrome Pathophysiology
Authors: Marzoog Basheer 
Published: September 2021

Abstract:
Undeniably, lipid plays an extremely important role in the homeostasis balance since
lipid contributes to the regulation of the metabolic processes. The metabolic syndrome pathogenesis
is multi-pathway that composes neurohormonal disorders, endothelial cell dysfunction,
metabolic disturbance, genetic predisposition, in addition to gut commensal microbiota. The heterogenicity
of the possible mechanisms gives the metabolic syndrome its complexity and limitation of
therapeutic accesses. The main pathological link is that lipid contributes to the emergence of
metabolic syndrome via central obesity and visceral obesity that consequently lead to oxidative
stress and chronic inflammatory response promotion. Physiologically, a balance is kept between
the adiponectin and adipokines levels to maintain the lipid level in the organism. Clinically, extremely
important to define the borders of the lipid level in which the pathogenesis of the
metabolic syndrome is reversible, otherwise it will be accompanied by irreversible complications
and sequelae of the metabolic syndrome (cardiovascular, insulin resistance). The present paper is
dedicated to providing novel insights into the role of lipid in the development of metabolic syndrome;
hence dyslipidemia is the initiator of insulin resistance syndrome (metabolic syndrome).
Valorisation of Fruit & Vegetable Wastes: A Review
Authors: Zahid Anila , Khedkar Renu 
Published: September 2021

:
Fruits and vegetables play an important part in the diets of global human population.
During processing, the unused residues, such as peels, stalks, rinds, stem, leaves etc., come out
as waste. Due to the high moisture content of these perishable wastes, they undergo rapid decomposition
that leads to foul odour and growth of pathogens. Almost 30% of the loss occurs
at the supply, retail, consumer, post-harvest and processing level. The perishable waste like
peels, pomace, seeds etc., act as threat to the environment and degrade pollution-free model.
The wastes are rich in protein, carbohydrates, minerals, vitamins and other phytochemicals and
bioactive compounds, such as pigments, dietary fibre, essential oils, etc. Recent researches
have shown that there is an increase in the utilization of these wastes for the extraction of value-
added products, such as bioactive compounds, bio-colorants, organic acids, single cell protein
(SCP), organic minerals, enzymes and others. The present review paper deals with the recent
studies conducted on the valorisation of the fruit & vegetable waste.
Development of Acid-Neutralization and In Vitro Dissolution to Evaluate
the Overall Quality of Compound Aluminum Hydroxide Tablets
Authors: Su Mengxiang , Yang Yuqing , Zhong Yuling , Xie Tingting 
Published: September 2021

Background:
Compound Aluminum Hydroxide Tablets (CAHTs) are widely used in
the Chinese domestic market, and strict quality control is required to ensure their clinical efficacy.

Purpose:
In this study, we established a comprehensive strategy of acid-neutralization, in vitro
dissolution and an assay of magnesium trisilicate to evaluate the overall quality and monitor the
consistency of CAHTs.

Methods:
The acid-neutralization profiles of 38 batches of CAHTs were generated using the
dissolution and release method III (the cup method, the Chinese pharmacopeia) combined with
potentiometric titration. To directly reflect the disintegration and release process of the preparation,
we optimized the sample pretreatment method by omitting the grinding step to determine
the profiles of complete tablets. In addition, in vitro dissolution was conducted in the hydrochloric
acid medium at pH 1.0 by using the assay of magnesium trisilicate through a validated approach
of Flame Atomic Absorption Spectrophotometry (FAAS) to evaluate the similarity of the
dissolution profiles.

Results:
Acid-neutralization tests showed that the quality of the samples from manufacturers B
and F was poor. In vitro dissolution experiments showed that the samples from manufacturer A
had the highest similarity with the reference preparation, which indicated their good quality consistency.
Besides, the optimized acid-neutralization method had the advantage of simple operation
and enabled direct characterization of pharmacodynamics in the quality consistency evaluation
of antacids.

Conclusion:
A successful synthetic evaluation strategy was established to assess the overall
quality of CAHTs, which demonstrated that the improvement in the quality of this formulation
is imperative.
Withdrawal Symptoms among Cigarette and Waterpipe Smokers: A Study in Natural Setting
Authors: Al-Shatnawi Samah F. , Alzoubi Karem H. , Khabour Omar F. 
Published: September 2021

Background:
The rates of tobacco use, including cigarette and waterpipe smoking, are surging in the Eastern Mediterranean region. The use of these products causes nicotine dependence that makes even short-term tobacco abstinence difficult due to aversive symptoms. During the daytime fasting of the month of “Ramadan”, people accept significant disruption in regular activities, including tobacco smoking. Thus, daytime during Ramadan (before sunset) is likely associated with abstinence symptoms emerging among tobacco smokers. We assessed this hypothesis by measuring tobacco/nicotine abstinence symptoms and craving among smokers of cigarettes or waterpipes during Ramadan.

Methods:
A cross-sectional survey-based study was conducted on a convenience sample of adults. Participants were assessed for general information about tobacco smoking, dependence, and nicotine desire or craving, and withdrawal symptoms using the Minnesota Nicotine Withdrawal Scale (MNWS) and the Tiffany-Drobes Questionnaire on Smoking Urges.

Results:
The study sample included 632 exclusive cigarette smokers and 161 exclusive waterpipe tobacco smokers. After fasting and abstaining from tobacco during the day, approximately 75% of cigarette smokers and 20% of waterpipe smokers reported smoking within the first 30 minutes. In addition, 10% of cigarette smokers and 30% of waterpipe smokers reported smoking within the first 60 minutes. Regarding smoking urge, no significant difference was found between cigarette and waterpipe smokers. For nicotine craving and withdrawal, significant differences between cigarette and waterpipe smokers were found when comparing mean scores for each of the following items: (i) urge to smoke, (ii) craving nicotine, (iii) hunger, (iv) desire for sweets, and (v) depression/feeling blue (P-values < 0.05).

Conclusion:
This study provided evidence from the month of Ramadan that waterpipe smoking is associated with abstinence-induced smoking urge and withdrawal symptoms that are comparable to cigarette smoking. More interdisciplinary research must be focused on developing interventions to reduce tobacco smoking, including waterpipe.
Recent Developments in Oxazole Derivatives as Anticancer Agents: Review on
Synthetic Strategies, Mechanism of Action and SAR Studies
Authors: Jaitak Vikas , Kulkarni Swanand , Kaur Kamalpreet 
Published: September 2021

Background:
Cancer is the world’s third deadliest disease. Despite the availability of numerous treatments,
researchers are focusing on the development of new drugs with no resistance and toxicity issues. Many newly synthesized
drugs fail to reach clinical trials due to poor pharmacokinetic properties. Therefore, there is an imperative requisite
to expand novel anticancer agents with in vivo efficacy.

Objective:
This review emphasizes synthetic methods, contemporary strategies used for the inclusion of oxazole moiety,
mechanistic targets, along with comprehensive structure-activity relationship studies to provide perspective into
the rational design of highly efficient oxazole-based anticancer drugs.

Methods:
Literature related to oxazole derivatives engaged in cancer research is reviewed. This article gives a detailed
account of synthetic strategies, targets of oxazole in cancer, including STAT3, Microtubules, G-quadruplex, DNA
topoisomerases, DNA damage, protein kinases, miscellaneous targets, in vitro studies, and some SAR studies.

Results:
Oxazole derivatives possess potent anticancer activity by inhibiting novel targets such as STAT3 and Gquadruplex.
Oxazoles also inhibit tubulin protein to induce apoptosis in cancer cells. Some other targets such as DNA
topoisomerase enzyme, protein kinases, and miscellaneous targets including Cdc25, mitochondrial enzymes, HDAC,
LSD1, HPV E2 TAD, NQO1, Aromatase, BCl-6, Estrogen receptor, GRP-78, and Keap-Nrf2 pathway are inhibited by
oxazole derivatives. Many derivatives showed excellent potencies on various cancer cell lines with IC50 values in
nanomolar concentrations.

Conclusion:
Oxazole is a five-membered heterocycle, with oxygen and nitrogen at 1 and 3 positions, respectively. It is
often combined with other pharmacophores in the expansion of novel anticancer drugs. In summary, oxazole is a promising
entity to develop new anticancer drugs.
Association of Perceived Gender Conflict with Depression and Attempted Suicide in Adolescent Girls
Authors: Catalan Liat Haruvi , Klomek Anat Brunstein , Shoval Gal , Zalsman Gil , Schapir Lior , Shechner Tomer , Krispin Orit , Horesh Neta , Apter Alan , Fennig Silvana 
Published: September 2021

Background and Goals:
Suicide attempts occur mostly during
adolescence and are much more frequent in females than in males, although males
tend to commit suicide more often than females. This study aims to examine the
association between female gender, gender conflict, depression, stress and suicide
attempts in adolescent girls.

Methods:
Participants included 86 adolescent girls aged 12-21 (μ=15.7, SD=3.07)
with depression (n=29), attempted suicide (n=15) or both (n=42), admitted
consecutively to a tertiary medical center and 93 healthy controls from the
community. Depression, suicidal ideation and behavior, gender identity and
conflict, personality factors, and stress were compared between the study group and
controls and each of the three study-subgroups and controls.

Results:
A difference was found in the perception gap of own femininity versus
others' expectations of the subject’s femininity, between the suicide attempters both
with and without depression and the controls. Personality factors were also found to
be related to depression and suicide attempts. Suicide attempters with depression
showed more harm avoidance than those without depression. Novelty seeking was
significantly higher in non-depressed suicide attempters than in controls but not
when compared to suicide attempters with depression.

Conclusion:
It seems that suicide attempts and depression may not only be related to
female gender identity. Conflicting gender expectations may result in increased stress,
raising the risk for suicide attempts, particularly in girls with high harm avoidance.
Neuroprotective Activities of Orientin: A Review
Authors: Sajini Deepak Vasudevan , Krishnamurthy Praveen Thaggikuppe , Kandiyil Amritha Chakkittu 
Published: September 2021

:
Orientin is a flavonoid C-glycoside found in many plants, and studies investigating its
neuropharmacological benefits have received significant attention in recent years. Orientin has modulating
effects on various neuropathological pathways such as Nrf2-ARE, PI3K/Akt, JNKERK1/
2, and TLR4/NF-kB. Orientin, therefore, is evaluated for its benefits in various neurodegenerative
diseases such as Alzheimer's and Huntington's disease. This paper reviews Orientin's neuroprotective
mechanisms and benefits.
Web-Based Behavioral Intervention Utilizing Narrative Persuasion for HIV Prevention Among Chinese Men Who Have Sex With Men (HeHe Talks Project): Intervention Development
Authors: Xin Meiqi , Coulson Neil S , Jiang Crystal Li , Sillence Elizabeth , Chidgey Andrew , Kwan Norman Nok Man , Mak Winnie W S , Goggins William , Lau Joseph Tak Fai , Mo Phoenix Kit Han 
Published: September 2021

Background
In the era of potent antiretroviral therapy, a high level of condomless anal intercourse continues to drive increases in HIV incidence in recent years among men who have sex with men. Effective behavior change strategies for promoting HIV-preventive behaviors are warranted. Narrative persuasion is a novel health communication approach that has demonstrated its persuasive advantages in overcoming resistance to counterattitudinal messages. The efficacy of narrative persuasion in promoting health behavior changes has been well documented, but critical research gaps exist for its application to HIV prevention.

Objective
In this study, we aimed to (1) capitalize on narrative persuasion to design a web-based multisession intervention for reducing condomless anal intercourse among men who have sex with men in Hong Kong (the HeHe Talks Project) by following a systematic development process; and (2) describe the main components of the narrative intervention that potentially determine its persuasiveness.

Methods
Persuasive themes and subtopics related to reducing condomless anal intercourse were initially proposed based on epidemiological evidence. The biographic narrative interview method was used to elicit firsthand experiential stories from a maximum variation sample of local men who have sex with men with diverse backgrounds and experiences related to HIV prevention; different types of role models were established accordingly. Framework analysis was used to aggregate the original quotations from narrators into collective narratives under 6 intervention themes. A dedicated website was finally developed for intervention delivery.

Results
A series of video-based intervention messages in biographic narrative format (firsthand experiential stories shared by men who have sex with men) combined with topic-equivalent argumentative messages were produced and programmed into 6 intervention sessions. The 6-week intervention program can be automatically delivered and monitored online.

Conclusions
We systematically created a web-based HIV prevention intervention derived from peer-generated stories. Strategies used to enhance the efficacy of the narrative intervention have been discussed within basic communication components. This paper describes the methods and experiences of the rigorous development of a narrative communication intervention for HIV prevention, which enables replication of the intervention in the future.