bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2: Possible Factors Contributing to Serious Consequences of
COVID-19?
Authors: Siddiqui Ruqaiyyah , Mungroo Mohammad R. , Abouleish Mohamed Y. , Khan Naveed A. 
Published: December 2021

Background and Objectives:
The recently discovered coronavirus, SARS-CoV-2 has infected over 170 million people (as of 31th May 2021) since it was elucidated in December
2019. The number of SARS-CoV-2 cases and mortality rates vary from country to country, and unfortunately, the United Kingdom ranks in the top
5 countries with the most deaths as of 31th May 2021.

Methods:
A literature review was conducted during May 2021 to examine if factors such as gut microbiome, ethnic diversity, high cancer rates, obesity and
alcohol consumption may have contributed to the higher number of cases and mortality due to SARS-CoV-2 in the UK.

Results:
The western diet is associated with a less diverse gut microbiome, as well as obesity, and contributes to the severity of SARS-CoV-2 infection.
Moreover, people belonging to Black and South Asian ethnic groups in the UK have an increased risk of death due to SARS-CoV-2 infection.
Given the high number of cancer patients in the UK, as well as excess consumption of alcohol, higher mortality rates were observed, most likely
due to people possessing a less diverse gut microbiome and/or weakened immune system.

Conclusion:
Targeting the gut microbiome in developing potential therapeutics against SARS-COV-2 is of value, and further studies are needed to understand
the specific role of the gut microbiome.
The Discrepancy between Gross Features and Chemical Compositions in
Gallbladder Stone: A Descriptive Single Center Study in the United Arab
Emirates
Authors: Cha Byung Hyo , Park Min Jung , Baeg Joo Yeong , Lee Sunpyo , Ahn Young Joon , Al Salami Wafaa Salem Obaid , Idris Osama Mohamed Ibrahim , Hong Duckjin , Kim Byoungkwon , Park Hyo Jin 
Published: December 2021

Background and Study Aim:
Gallbladder stone (GBS) is a common gastrointestinal disease that is the primary indication for cholecystectomy. The present study was conducted
to describe the chemical composition of gallstones in a tertiary referral hospital in the United Arab Emirates.

Materials and Methods:
Patients diagnosed with GBS and who underwent cholecystectomy due to symptomatic GBS and cholecystitis in Sheikh Khalifa Specialty Hospital
were enrolled in this study. After cholecystectomy, all stone specimens were classified according to their gross findings into 4 groups, namely
black pigmented stones (BLPS), brown pigmented stones (BRPS), mixed cholesterol stones, and cholesterol stones (CLS). Quantitative analysis
using Fourier transform infrared spectroscopy was then performed to define the stones’ chemical constituents. They were reclassified into two
groups as CLS (cholesterol ≥ 60%) and pigmented stones (PGS, cholesterol ≤ 59%) based on gallstone composition analysis.

Results:
A total of 237 stones were divided into four groups based on their gross findings; cholesterol stones (32.0%), mixed cholesterol (29.2%), black
pigmented (26.4%), and brown pigmented (12.3%). After chemical composition analysis, they were resorted into the two following groups
according to their cholesterol proportions: pigmented (28.3%) and cholesterol (71.7%). There were significant statistical mean age differences
between the pigmented and cholesterol stone groups (58.5±19.8 vs. 34.4±11.0, p < 0.01).

Conclusion:
This descriptive study showed the hospital-based clinical incidence of GBS and suggested that there might be a discrepancy in stone classification
based on gross findings and chemical compositions. Moreover, pigmented stones are more likely to be present in older patients than cholesterol
stones.
A Review of the Rational and Current Evidence on Colchicine for COVID-19
Authors: Ghaith Hazem S. , Gabra Mohamed Diaa , Nafady Mohamed H. , Elshawah Hamza Emad , Negida Ahmed , Mushtaq Gohar , Kamal Mohammad Amjad 
Published: December 2021

Abstract:
The current coronavirus disease (COVID-19) pandemic has affected millions of individuals worldwide.
Despite extensive research efforts, few therapeutic options currently offer direct clinical benefits for
COVID-19 patients. Despite the advances in our understanding of COVID-19, the mortality rates remain significantly
high owing to the high viral transmission rates in several countries and the rise of various mutations in
the SARS-CoV-2. One currently available and widely used drug that combines both anti-inflammatory and immunomodulatory
actions is colchicine, which has been proposed as a possible treatment option for COVID-19.
Colchicine still did not get much attention from the medical and scientific communities despite its antiinflammatory
and immunomodulatory mechanisms of action and positive preliminary data from early trials.
This literature review article provides the scientific rationale for repurposing colchicine as a potential therapy
for COVID-19. Further, we summarize colchicine’s mechanisms of action and possible roles in COVID-19 patients.
Finally, we supplement this review with a summary of the doses, side effects, and early efficacy data
from clinical trials to date. Despite the promising early findings from multiple observational and clinical trials
about the potential of colchicine in COVID-19, the data from the RECOVERY trial, the largest COVID-19 randomized
controlled trial (RCT) in the world, showed no evidence of clinical benefits in mortality, hospital
stays, or disease progression (n = 11340 patients). However, multiple other smaller clinical trials showed significant
clinical benefits. We conclude that while current evidence does not support the use of colchicine for treating
COVID-19, the present body of evidence is heterogeneous and inconclusive. The drug cannot be used in
clinical practice or abandoned from clinical research without additional large RCTs providing more robust evidence.
At present, the drug should not be used except for investigational purposes.
A Randomized Trial of Short-term Treatment with Folic Acid to Reduce the
Oxidative Stress of Patients with Chronic Kidney Disease
Authors: Matsumoto Andressa Keiko , Michelin Ana Paula , Semeão Laura de Oliveira , Sepúlveda-Loyola Walter , de Lima Pedrão João Victor , Porto Guilherme Martins , Arceni Beatriz Suellen , Moreira Estefânia Gastaldello , Delfino Vinicius Daher Alvares , Barbosa Décio Sabbatini 
Published: December 2021

Background:
Increased generation of reactive oxygen and nitrogen species in chronic kidney disease
(CKD) patients leads to increased oxidative stress. The antioxidant capacity of folic acid has been shown to scavenge
radicals efficiently.

Objective:
The current study was carried out to examine the effects of folic acid treatment on biochemical and oxidative
stress biomarkers in patients in different stages of CKD.

Methods:
This was a randomized, non-blinded, clinical trial that assessed the effects of 3 months of treatment with 5
mg of folic acid daily or no treatment in 113 outpatients within CKD stages 3a and 3b. At the end of the intervention,
we analyzed the data of 66 patients treated with folic acid and 47 in the control group. Serum homocysteine levels
and biochemical and oxidative/nitrosative stress biomarkers were analyzed in all patients.

Results:
In most patients, folic acid treatment normalized homocysteine levels and increased antioxidant enzyme
activity (paraoxonase 1) and decreased sulfhydryl (SH) groups. In addition, oxidative biomarkers (products of nitric
oxide and lipid hydroperoxide) were significantly lower post-treatment compared to baseline in the active intervention
group. In the no active intervention group, no statistically significant effects were found on the oxidative and
biochemical biomarkers.

Conclusion:
Folic acid treatment in stages 3a-4 CKD patients effectively ameliorated their hyperhomocysteinemia
and increased the activity of antioxidant enzymes, as well as decreased the levels of pro-oxidant biomarkers in stage
G3a and G3b CKD patients. Folic acid treatment attenuated oxidative/nitrosative stress and may be considered as a
possible strategy to improve redox status and diminish the damages associated with oxidative/nitrosative stress in
CKD patients. Further studies are needed to confirm these findings.

Clinical Trials Register No:
This study is registered in the Brazilian Record of Clinical Trials (ReBEC), under reference
RBR-2bfthr.
Regulatory mechanism of the SNHG3/miR-302a-3p/E2F1 feedback loop in nerve repair post cerebral ischemic stroke
Authors: Sun Xiaoyu , Wang Lizhou , Huang Xueqing , Zhou Shi , Jiang Tianpeng 
Published: December 2021

Objective:
Cerebral ischemic stroke (CIS) remains a primary cause of death worldwide. The current knowledge has identified the implication of microRNAs (miRNAs) in the pathophysiology of CIS. This study investigated the mechanism of miR-302a-3p in nerve repair post-CIS.

Methods:
A middle cerebral artery occlusion (MCAO) model was established in mice to simulate CIS. miR-302a-3p expression in brain tissues of MCAO mice was up-regulated by injecting agomiR-302a-3p. The neurological deficit of MCAO mice was evaluated through neurological function score, forelimb placing test, and balance beam walking test. Neuronal damage was measured using Nissl staining. The concentrations of nerve injury-related factors (S100B and GFAP) and the contents of neuroinflammatory factors (TNF-α and IL-1β) in serum were examined using ELISA kits. miR-302a-3p, E2F1, and long non-coding RNA (lncRNA) SNHG3 expressions in brain tissues of MCAO mice were determined using RT-qPCR and Western blot. The binding relationships between miR-302a-3p and E2F1 and E2F1 and SNHG3 were validated using dual-luciferase and ChIP assays, respectively.

Results:
miR-302a-3p expression was reduced in brain tissues of MCAO mice. miR-302a-3p overexpression increased the number of neurons, decreased the concentrations of S100B and GFAP, reduced the contents of TNF-α and IL-1β, promoted nerve repair, and alleviated CIS-induced brain injury. miR-302a-3p targeted E2F1 expression, and E2F1 activated SNHG3 transcription. E2F1 overexpression or SNHG3 overexpression reversed the effect of miR-302a-3p overexpression on nerve repair in MCAO mice.

Conclusion:
miR-302a-3p overexpression repressed SNHG3 transcription by targeting E2F1 expression, thereby promoting nerve repair and alleviating CIS.
Gabapentin Antioxidant Derivatives with Anti-Inflammatory and Neuroprotective
Potency
Authors: Papagiouvannis Georgios , Theodosis-Nobelos Panagiotis , Tziona Paraskevi , Gavalas Antonios , Kourounakis Panos N. , Rekka Eleni A. 
Published: December 2021

Aims:
The aim of this work is to investigate the antioxidant and anti-inflammatory potency of
novel gabapentin derivatives, which could be proven useful as neuroprotective agents.

Background:
Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders worldwide.
Due to its multi-factorial character, no effective treatment has been obtained yet. In this direction,
the multi-targeting compounds approach could be useful for the development of novel, more effective
drugs against AD. Oxidative stress and inflammation are highly involved in the progression of neurodegeneration,
while gabapentin has been investigated for the treatment of behavioral symptoms in AD.

Objective:
In this work, derivatives of cinnamic acid, Trolox, and 3,5-di-tertbutyl-4-hydroxybenzoic acid
amidated with gabapentin methyl ester were designed and studied. Compounds with these structural characteristics
are expected to act in various biochemical pathways, affecting neurodegenerative processes.

Methods:
The designed compounds were synthesized with classical amidation methods, purified by flash
column chromatography, and identified spectrometrically (1H-NMR and 13C-NMR). Their purity was
determined by CHN elemental analysis. They were tested in vitro for their antioxidant and antiinflammatory
properties and for their inhibitory effect on acetylcholinesterase. Their in vivo antiinflammatory
activity was also tested.

Results:
Molecules that incorporated antioxidant moiety possessed inhibitory activity against rat microsomal
membrane lipid peroxidation and oxidative protein glycation, as well as radical scavenging activity.
Moreover, most of them presented moderate inhibition towards lipoxygenase (up to 51% at 100μΜ)
and acetylcholinesterase (AchE) (IC50 up to 274μΜ) activities. Finally, all synthesized compounds presented
in vivo anti-inflammatory activity, decreasing carrageenan-induced rat paw edema up to 53%, and
some of them could inhibit cyclooxygenase significantly.

Conclusion:
These results indicate that the designed compounds could be proven useful as multitargeting
molecules against AD since they affect various biochemical pathways associated with neurodegeneration.
Thus, more effective drugs can be obtained, and the possible adverse effects of drug combinations
can be limited.
Treatment Outcomes of the Standardized Shorter MDR-TB Regimen Under
Programmatic Setting: A Retrospective Study from a Tertiary Care
Centre, India
Authors: Swapna R. , Swathi K.M.P , Somashekar M. , Chakraborty A. , Akshata J.S. , Nagaraja C. 
Published: December 2021

Background:
The shorter regimen was widely accepted and advocated for MDR-TB
treatment compared tothe conventional longer regimen. Evaluating the performance of both regimens
in a programmatic setting will help in tailoring the treatment regimen of MDR-TB.

Objectives:
To estimate the duration of sputum smear conversion in the shorter MDR-TB regimen.
2. To compare the treatment outcomes of the shorter MDR-TB regimen with that of the longer conventional
MDR regimen in a programmatic set up in India. 3. To estimate the adverse drug reactions
in the shorter MDR-TB regimen.

Methods:
A retrospective cross-sectional study was conducted on 320 patients enrolled under programmatic
management of drug resistant tuberculosis (PMDT) from April 2017 to May 2019 at a
nodal DRTB center and a tertiary care hospital in India. Demographic and clinical characteristics
of those who received a shorter MDR-TB regimen were recorded. Treatment outcomes of both regimens
were recorded. Treatment success is defined as ‘disease cured and treatment completed’,
whereas treatment failure was considered when the treatment was either terminated or changed due
to lack of bacteriological conversion at the end of an extended intensive phase or culture reversion
in the continuation phase.

Results:
The treatment success observed in the shorter MDR-TB regimen was 61.25%, which was
significantly higher than the conventional longer regimen (p=0.0007). Treatment failures were higher
with a shorter MDR-TB regimen (p=0.0001).

Conclusion:
Treatment success with the shorter MDR-TB regimen though higher than the conventional
regimen, is still way behind the target treatment success rate. Improving treatment adherence
remains pivotal for achieving end TB targets.
Design, Synthesis and Biological Evaluation of Coumarin Derivatives as NEDD8 Activating Enzyme Inhibitors in Pancreatic Cancer Cells
Authors: Gong Lei , Lu Peng , Lu Cheng , Li Mengli , Wan Huiyang , Wang Yubin 
Published: December 2021

Background:
NEDD8 (neural precursor cell expressed developmentally downregulated
protein 8) is one of the ubiquitin-like proteins which is activated by the NEDD8 activating enzyme
(NAE). The overexpressed NAE can cause a variety of diseases such as numerous cancer types and
inflammatory diseases. The selective inhibition of NAE could mediate the rate of ubiquitination and
the subsequent degradation of proteins associated with cancer so as to achieve the purpose of treatment.

Objective:
In this article, we decided to study the synthesis and screening of coumarin scaffold derivatives
against cancer cell lines, specifically the human pancreatic cancer cell line BxPC-3.

Methods:
Twenty-four targeted compounds were synthesized, and their anti-proliferative activity
against three cancer cell lines, cytotoxicity against three normal cell lines through CCK-8 and MTT
assay were evaluated to screen out the candidate compound. Then the target was further confirmed
by both enzyme and cell-based experiments, as well as cell apoptosis research.

Results:
Several new 4-position substituted coumarin derivatives (12a~x) were synthesized and most
of them exhibit antiproliferative activity in three cancer cell lines. A series of experiments were performed
to identify the best candidate compound 12v. This compound displayed the highest potency
against BxPC-3 with an IC50 value of 0.28 μM. It can also inhibit NAE activity in enzyme and cellbased
assay, and induce CRLs-mediated accumulation of the substrate and apoptosis in BxPC-3
cells. Meanwhile, it exhibited relatively low toxicity in three normal cells.

Conclusion:
Based on these results, we found that compound 12v inhibited NAE activity in enzyme
and cell-based systems and induced apoptosis in BxPC-3 cells. Additionally, it also had a low toxicity.
These results suggested that 12v may be promising lead compounds for the development of new
anticancer drugs.
Preparation of Chitosan Particles as a Delivery System for Tetrahydrocurcumin: β-cyclodextrin Inclusive Compound for Colorectal Carcinoma
Authors: Fai Tan Kin , Yee Goh Hui , Kumar Palanirajan Vijayaraj , Elumalai Manogaran 
Published: December 2021

Background:
Tetrahydrocurcumin is a hydrogenated active metabolite of curcumin that
exhibits similar pharmacological effects to curcumin. However, its hydrophobic nature has limited its
aqueous solubility and bioavailability. By incorporating the tetrahydrocurcumin into β-cyclodextrin,
its physiochemical property can be improved.

Objective:
To develop a chitosan composite loaded with tetrahydrocurcumin inclusive complex, characterize
the developed composites, and evaluate its effectiveness on cancer cells.

Methods:
Tetrahydrocurcumin was formulated into an inclusive complex with β-cyclodextrin in the
ratio of 1:2 (Tetrahydrocurcumin: β-cyclodextrin). The tetrahydrocurcumin inclusive complex loaded
chitosan particles (THC IC-loaded CPs) were prepared using ionic gelation and later characterized using
FTIR. Cytotoxicity of THC IC-loaded CPs in human colon cancer cells, Caco-2 cells, was examined
using RTCA xCELLigence technology. The uptake of these particles by Caco-2 cells was also
evaluated via fluorescing microscopy.

Results:
FTIR results confirmed the formation of the tetrahydrocurcumin inclusive complex and the
loading of this complex into chitosan composites. The cytotoxic effect of THC IC-loaded CPs showed
a dose-dependent relationship, and the IC50 found was 1.117mM and 0.959mM after 48 and 72 hours,
respectively. THC IC-loaded CPs showed an immediate uptake by CaCo-2 cells, and the maximum
uptake was observed after 1 hour of incubation.

Conclusion:
This study showed that THC IC-loaded CPs is a potential drug carrier to deliver tetrahydrocurcumin
into cancer cells and able to produce a cytotoxic effect on cancer cells.
The Impact of Polyphenolics in the Management of Breast Cancer:
Mechanistic Aspects and Recent Patents
Authors: El-Nashar Heba A.S. , Aly Shaza H. , Ahmadi Amirhossein , El-Shazly Mohamed 
Published: December 2021

Background:
Breast cancer is the most frequently diagnosed type of cancer in women, accounting for 2.1 million cases, and stands as the fifth leading cause of death. Several treatment strategies are available, such as surgical resection, radiation, hormonal therapy, and conventional chemotherapy; however, these are associated with severe adverse effects in the patients.

Objective:
This review aims to summarize the different studies (in vitro, in vivo, and new patents) concerning the therapeutic potential of plant polyphenolics in the management of breast cancer, published in the period from January 2016 to January 2021. Moreover, this review will focus on the underlying mechanisms of action and molecular characteristics of these compounds.

Methods:
The data of this review were collected from different scientific databases, such as Pub-Med, Science Direct, Google Scholarship, SciFinder, and Egyptian Knowledge Bank (EKB).

Results:
During the period 2016-2021, in the in vitro studies, investigation on 52 compounds of polyphenolic nature with promising anti-breast cancer activity has been conducted, while 14 com-pounds have been reported via in vivo studies. Besides, about 15 compounds have been registered as patent drugs. Different mechanisms of action and molecular targets have been reported, provid-ing a clarified basis and precise reflection of the anticancer properties of these compounds against breast cancer.

Conclusion:
Polyphenolics represent a comprehensive source of anticancer lead compounds against the progression of breast cancer invasion and metastasis.
Perbedaan Lemak Jenuh dan Tak Jenuh Keripik Labu Kuning Metode Vacuum Frying dengan Menggunakan Minyak Berulang
Authors: Kusuma Titis Sari , Kurniawati Adelya Desi , Firmansyah Rizal Fakih , Septiana Elly 
Published: December 2021

Masyarakat saat ini cenderung untuk mengonsumsi fast food yang mengandung tinggi kalori, rendah serat, tinggi lemak jenuh dan kolesterol yang dapat memicu terjadinya sindrom metabolik salah satunya dislipidemia. Labu kuning memiliki kadar kolesterol rendah dan pengolahan menjadi keripik dengan metode Vacuum Frying bertujuan untuk mempertahankan kualitas bahan pangan dan mengurangi kerusakan pada minyak goreng akibat hidrolisis. Tujuan dari penelitian ini adalah untuk mengetahui perbedaan kadar asam lemak jenuh dan tak jenuh keripik labu kuning metode Vacuum Frying dengan penggunaan minyak berulang pada kelipatan penggorengan ke 1, ke 5 dan ke 10.Â Metode penelitian ini bersifat Quasi Eksperimental dengan 3 kelompok dan 2 kali replikasi. Pengujian kadar asam lemak jenuh menggunakan metode GC FID dan asam lemak tak jenuh dengan metode kromatografi gas. Data dianalisa menggunakan SPSS Versi 21.0 dengan uji shapiro wilk dilanjutkan uji kruskal wallis. Hasil penelitian ini adalah tidak ada perbedaan kadar asam lemak jenuh (p>0,05), tidak ada penurunan kadar asam palmitoleat (p=0,565) , asam alpha linolenat (p=0,156 ) dan asam gamma linolenat (p=0,276) pada keripik labu kuning. Karena tidak ada perubahan kadar asam lemak jenuhÂ dan tak jenuh, maka keripik labu kuning dapat dijadikan alternatif snack bagi penderita dislipidemia.Â