bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Ferrocene Formates Bearing Isoxazole Moieties: Synthesis, Characterization,
X-ray Crystallography, and Preliminarily Cytotoxicity against A549, HCT116, and
MCF-7 Cell Lines
Authors: Yong Jianping , Lu Canzhong , Yang Minxue , Wu Xiaoyuan 
Published: August 2022

Aims:
To develop new anticancer agents based on ferrocene core.

Background:
Cancer has become the major cause of human death globally. The death caused by cancer mainly
focuses on lung cancer, breast cancer, liver cancer, carcinoma of the colon, and rectum. Some small molecular
inhibitors have been authorized by FDA for the treatment of cancer and several candidates are in different phases
of clinical trials. However, cancer chemotherapy is still highly inadequate. Thus, it is indispensable to develop
novel anticancer agents.

Objective:
Based on the previous good results, twelve novel structures of ferrocene formates bearing isoxazole
moiety (3a-3l) were synthesized in this work for the development of anticancer agents.

Methods:
The target compounds were synthesized using Ferrocenecarboxylic acid and 3-[(R)-substitutedphenyl]-
isoxazole-5-methanol catalyzed by DCC and DMAP. The structures of target compounds were characterized
by 1H NMR, 13C NMR, MS, HR-MS and XRD. Then, their preliminarily in vitro cytotoxicity against
A549, HCT116, and MCF-7 cell lines was evaluated using the MTT method.

Results:
The results showed that most compounds exhibited moderate cytotoxicity against A549, HCT116, and
MCF-7 cell lines compared with the positive control gefitinib. However, (3b, 3c, 3e, 3j, and 3k) simultaneously
exhibited stronger inhibitory activity against A549, HCT116, and MCF-7 cell lines, which can be regarded as
promising metal-based lead compounds for the development of anticancer agents.

Conclusion:
In this work, twelve new structures of ferrocene derivatives containing isozaole moiety were
synthesized and their cytotoxicity against 549, HCT116, and MCF-7 cell lines was evaluated. (3b, 3c, 3e, 3j,
and 3k) simultaneously exhibited stronger inhibitory activity towards A549, HCT116, and MCF-7 cell lines,
which can be regarded as promising metal-based lead compounds for the development of anticancer agents.
The Role of Dehydroepiandrosterone in Improving in vitro Fertilization
Outcome in Patients with DOR/POR: A Systematic Review and Meta-
Analysis
Authors: Qu Bing , Wang Jing , Liu Bowen , Wen Jing 
Published: August 2022

Background and Objective:
Although many trials have evaluated the use of dehydroepiandrosterone
to improve outcomes in poor responders undergoing assisted reproductive technology
treatment, evidence supporting this approach is controversial. We aimed to conduct a systematic
review and meta-analysis of existing published data to further elucidate and supplement the use of
Dehydroepiandrosterone (DHEA) to improve the effectiveness of vitro fertilization in patients with
diminished ovarian reserve or adverse ovarian reactions.

Methods:
PubMed, Embase, Cochrane Library, and the Web of Science databases were searched
through December 2020. Oocyte yield, metaphase II oocytes, fertilized oocytes, top-quality embryos,
clinical pregnancy rate, ongoing pregnancy rate, and live birth rate were analyzed as relative outcomes.
Meta-analysis was performed and fitted to both fixed-effects models and random-effects models.

Results:
Eight prospective randomized controlled studies, five prospective case-control studies, and
three retrospective cohort studies were conducted with a total of 1998 participants. Meta-analyses of
these studies showed a significantly higher number of oocytes retrieved (WMD 1.09, 95% CI 0.38
to 1.80), metaphase II oocytes (WMD 0.78, 95% CI 0.16 to 1.40), fertilized oocytes (WMD 0.84,
95% CI 0.42 to 1.26), top-quality embryos (WMD 0.60, 95% CI 0.34 to 0.86), clinical pregnancy
rate (RR 1.35, 95% CI 1.13 to 1.61), and ongoing pregnancy rate (RR 1.82, 95% CI 1.34 to 2.46),
although there was no difference in live birth rate (RR 1.35, 95% CI 0.94 to 1.94) in the DHEA supplementation
groups compared with that in the control groups.

Conclusion:
Oral DHEA supplementation appears to improve some IVF outcomes. On the basis of
this limited evidence, we conclude that further studies are required to provide sufficient data.
Identification of the Origin, Authenticity and Quality of Panax Japonicus
Based on a Multistrategy Platform
Authors: Qiu Ziying , Zhao Xiaoran , Liu Meiqi , Liu Yanan , Sun Lili , Ren Xiaoliang , Deng Yanru 
Published: August 2022

Background:
Panax Japonicus (PJ) is a widely used Chinese herbal medicine, functional
food and tonic. However, its origin has a great influence on the quality of PJ, and with the increasing
demand for PJ, fake and inferior products, such as Panax Stipuleanatus (PS), often appear. The
identification of the origin and authenticity of PJ is critical for ensuring the quality, safety and effectiveness
of drugs.

Objective:
Proposing a strategy to identify the origin, authenticity, and quality of PJ using HPLC
fingerprints, chemometrics, and network pharmacology.

Method:
The chromatographic fingerprint method was established to analyze the origin and authenticity
of PJ. Multiple chemometric methods were performed to analyze the fingerprints, including
a Hierarchical Cluster Analysis (HCA), Principal Component Analysis (PCA), and Counter
Propagation Artificial Neural Network (CP-ANN). Finally, the network pharmacology method was
used to construct the "active ingredient-target" network, predict and assist in analyzing potential Qmarkers
in PJ.

Result:
Ward’s method was used for the HCA. The results showed that PJ samples from different
origins had significant regional differences and could be accurately distinguished from PS. The
PCA classification results are consistent with the HCA classification results, further illustrating the
model's accuracy. The CP-ANN model can analyze and predict PJ and PS and accurately obtain PJ
and PS chemical markers to identify PJ and PS correctly. The network pharmacology of PJ was
constructed, and three PJ Q-markers, namely, ginsenoside Ro, ginsenoside Rb1, and chikusetsu saponin
Ⅳa, were identified, which lays a foundation for the establishment of PJ quality standards.

Conclusion:
This research provides a feasible platform for the quality evaluation of PJ in the future.
Recreational Cannabis Use: Regulatory Aspects, Public Opinion and
Concerns for Public Health
Authors: Scopetti Matteo , Padovano Martina , Peruch Michela , Concato Monica , Livieri Tommaso , Radaelli Davide , D’Errico Stefano 
Published: August 2022

Abstract:
Cannabis represents the most used substance in the young population after alcohol and tobacco. The consumption of the substance undoubtedly represents an emerging public health issue and the regulatory aspects are quite heterogeneous. Alternatives to drug prohibition, such as legalization or decriminalization, are a topic of growing debate among researchers, policy makers and the public. Limiting harmful use and combating illicit trafficking are the main objectives of legalization for recreational purposes, although liberalization raises critical issues that have not yet been resolved despite the experience gained in many countries. In the context of legalization, it is essential to allow the lawful production of cannabis, guarantee a supply of controlled quality cannabis, and ensure that the population understands the risks associated with the consumption of the substance. At the same time, it is essential to protect the safety and health of the population by limiting access to cannabis and preventing accidental exposure of fragile categories and children. Incomplete knowledge of law enforcement can create further complications. Incomplete knowledge of the implementation of the laws can create further complications therefore adequate information must be favored. Scientific evidence helps to understand the potential harms and benefits of cannabis, but the impact of legalization - even in terms of reducing consumption - is not clearly documented. So, far more efforts need to be made in the future to broaden awareness of the general population on the recreational use of cannabis.
Encapsulation of Anabolic Peptide in Lipid Nano Vesicles for Osteoporosis
Authors: Benival Derajram , Salave Sagar , Rana Dhwani 
Published: August 2022

Background:
Screening of critical variables, including formulation and process variables,
in the development of various dosage forms facilitates the identification of the most influencing parameters,
which modulate the responses, thereby helping in building the strong quality target product
profile.

Objective:
The objective of the present work was to screen out the most influential and critical variables
for the development of an anabolic peptide encapsulated lipid nanovesicles (PTH-LNVs).

Methods:
PTH-LNVs were prepared by the ethanol injection method. Taguchi standard orthogonal
array L8 design was employed to assess the effect of formulation and processing variables on different
response variables. Independent variables considered were drug concentration, lipid concentration,
cholesterol concentration, stirring rate, and rate of injection, whereas dependent variables studied
were particle size, PDI, zeta potential, % entrapment efficiency, and % drug loading. Particle
size, PDI, and zeta potential were evaluated by a zeta sizer. Drug loading efficiency and % entrapment
efficiency were determined by HPLC analysis.

Results:
The ethanol injection method was employed to formulate PTH-LNVs using Taguchi standard
orthogonal array L8 design. From the half-normal plot and Pareto ranking analysis, it was found
that drug, lipid, and cholesterol concentration have a significant effect on responses of formulation
and are hence considered critical variables during the formulation development.

Conclusion:
The presented work demonstrates the feasibility of Taguchi orthogonal array design in
the screening of potential independent factors in the development of peptide encapsulated nanoformulations.
Hydroxysafflor Yellow A-Induced Osteoblast Differentiation and
Proliferation of BM-MSCs by Up-Regulating Nuclear Vitamin D
Receptor
Authors: Pan Jiewen , Bao Youwei , Pan Shuqing , Zhuang Danyan , Xu Yanan , Pan Xiaoli , Li Haibo 
Published: August 2022

Background:
Vitamin D receptor (VDR) is critical for mineral and bone
homeostasis since it plays an essential role in the osteoblast differentiation of bone
marrow mesenchymal stem cells (BM-MSCs). Hydroxysafflor yellow A (HSYA) has the
potential to promote bone mineralization and inhibit bone resorption, while its detailed
mechanism needs to be elaborated.

Objective:
This study intends to explore the action of HSYA on the proliferation and
differentiation of BM-MSC and the underlying mechanism.

Method:
Different concentrations of HSYA to BM-MSC and CCK-8, and EdU were
used to detect cell viability and proliferation. The alkaline phosphatase (ALP) was used
to observe the differentiation ability of BM-MSC osteoblasts. The calcium uptake and
mineralization of osteoblast-like cells were observed by alizarin red staining. The level of
calcium ion uptake in cells was detected by flow cytometry. AutoDock was performed for
molecular docking of HSYA to VDR protein. Immunofluorescence and western blotting
were performed to detect the expression of VDR expression levels. Finally, the effect of
VDR was verified by a VDR inhibitor.

Result:
After treatment with HSYA, the proliferation and calcium uptake of BM-MSC
were increased. The level of ALP increased significantly and reached its peak on the
12th day. HSYA promoted calcium uptake and calcium deposition, and mineralization of
osteoblasts. The western blotting and immunofluorescence showed that HSYA
increased the expression of VDR in the osteoblast-like cell's nucleus and upregulated
Osteocalcin, S100 calcium-binding protein G, and CYP24A1. In addition, HYSA
treatment increased the expression of osteopontin and the synthesis of osteogenic
proteins, such as Type 1 collagen. After the addition of the VDR inhibitor, the effect of
HSYA was weakened.

Conclusion:
HSYA could significantly promote the activity and proliferation of
osteoblasts and increase the expression level of VDR in osteoblasts. HSYA may also
improve calcium absorption by osteoblasts by regulating the synthesis of calciumbinding
protein and vitamin D metabolic pathway-related proteins.
Association of Rebleeding and Delayed Cerebral Ischemia with Long-term
Mortality Among 1-year Survivors After Aneurysmal Subarachnoid Hemorrhage
Authors: Fang Fang , Wang Xing , Zhang Yu , Chong Weelic , Hai Yang , Wang Peng , Deng Haidong , You Chao 
Published: August 2022

Background and Objective:
The potential impact of rebleeding and delayed cerebral
ischemia (DCI) on long-term survival in patients with aneurysmal subarachnoid hemorrhage
(aSAH) remained unclear. This study aimed to investigate whether DCI and rebleeding increase the
risk of long-term all-cause mortality in patients with aSAH who survived the follow-up period of
one year.

Methods:
We retrospectively collected data on patients with atraumatic aSAH who were still alive
12 months after aSAH occurrence between December 2013 and June 2019 from the electronic
health system. Patients were then classified by the occurrence of rebleeding or DCI during hospitalization.
Death records were obtained from an administrative database, the Chinese Household Registration
Administration System, until April 20, 2021. Multivariable Cox proportional hazards models
were used to compare overall survival in different groups. Sensitivity analysis was performed with
propensity-score matching (PSM).

Results:
A total of 2,607 patients were alive one year after aSAH. The crude annual death rate from
any cause among patients who had rebleeding (7.2 per 100 person-years) and patients who had DCI
(3.7 per 100 person-years) during hospitalization was higher than that of patients with neither event
(2.1 per 100 person-years). Multivariate analysis showed that rebleeding is an independent risk factor
for long-term mortality (adjusted hazard ratio (aHR), 2.37; 95% confidence interval (CI), 1.47-
3.81). DCI was an independent prognostic factor of poorer overall survival (aHR, 2.09; 95% CI,
1.54-2.84).

Conclusions:
Amongst patients alive one year after aSAH, rebleeding and DCI during hospitalization
were independently associated with higher rates of long-term mortality.
The Effect of Acupuncture on Enteral Nutrition and Gastrointestinal
Dynamics in Patients Who Have Suffered a Severe Stroke
Authors: Tang Chun-Zhi , Qin Liang , Zhang Xin-Xin , Jin Xin , Cui Cai-Hong 
Published: August 2022

Objective:
This study aimed to explore and analyze the effect of acupuncture on improving the enteral
nutrition level and gastrointestinal dynamics in patients who had suffered a severe stroke.

Methods:
A total of 122 patients who experienced a severe stroke who were treated in the intensive care unit of
the Affiliated Hospital of Hebei University (China) between September 2021 and March 2022 were randomly
divided into two groups as follows: 1) the observation group, the participants of which received acupuncture
combined with early enteral nutrition (61 cases); 2) the control group, the participants of which received early
enteral nutrition (61 cases). Following treatment, the hemoglobin, neutrophil count, blood glucose, albumin, prealbumin,
immediate postprandial antral area, antral contraction frequency (at 2 min), and antral motility index on
days 1 and 7 of treatment were compared between the two groups.

Results:
The total clinical effective rate was 96.72% in the observation group and 77.05% in the control group.
The curative effect comparison between the two groups after seven days of treatment showed a lower probability
of gastrointestinal bleeding, faster recovery of gastrointestinal motility, and a higher level of nutrient absorption
in the observation group. Serum albumin, pre-albumin, hemoglobin, total lymphocyte count, immediate postprandial
maximum (max) and minimum (mix) area of the gastric antrum, antral contraction frequency (at 2 min),
and antral motility index were higher in the observation group than in the control group (P < 0.05). The difference
in blood glucose levels between the two groups was not statistically significant (P > 0.05).

Conclusion:
Acupuncture improved the enteral nutrition status of patients who had suffered a severe stroke and
promoted gastrointestinal motility. The combination of acupuncture and early enteral nutrition could reduce
damage to the gastrointestinal mucosal barrier caused by stress, changes in metabolism, and improved gastrointestinal
function.

Clinical Trial Registration Number:
The study was registered in China Clinical Trial Registration Center in
September 2021 (registration no. CHiCTR2100050740).
Research on the Necessity of AIDS Intervention for College Students Based
on Cognitive Behavioral Therapy
Authors: Yao Fei , Li Yin , Wang Qiang , Chen Lingxue , Xiang Xiaochen , Wan Yuting , Qin Junjie , Guo Jiaqi , Wang Jiadun , Zhang Wei 
Published: August 2022

Background:
Despite abundant research on AIDS prevention and intervention, many residual
factors influence the actual impact of the intervention at a population level. Misconceptions
held by subjects lead to patterns of behavior, which do not reflect levels of cognition.

Methods:
Cognition and behavioral patterns relating to HIV were investigated without intervention
in freshmen before and after a two-year study period. A total of 461 freshmen studying at the university
in Wuhan, Hubei Province, China, were enrolled in September 2019. Data management and
analysis were performed by SPSS 25.0 software.

Results:
Throughout the two years’ study, no significant changes in the cognitive level regarding
AIDS were found while the frequency of sexual behavior increased significantly. A trend of inconsistency
between cognition and behavior was identified.

Conclusions:
During a two-year period without intervention, it was found that the sexual behavior of
university students gradually increased, perceptions regarding AIDS-related subjects were incomplete
and awareness of HIV infection risk was still weak. A phenomenon described as the separation
of knowledge from behavior was detected. Misconceptions that influenced behavioral patterns were
identified as critical factors. Therefore, we propose that cognitive behavioral therapy may change
the actual impact of AIDS prevention interventions.
Design, Synthesis, Molecular Docking, ADMET, and Biological Studies of
Some Novel 1,2,3-Triazole Linked Tetrazoles as Anticancer Agents
Authors: Kishore Pilli Veera Venkata Nanda , Dunga Ananda Kumar , Allaka Tejeswara Rao , Kethavarapu Yugandhar , Nechipadappu Sunil Kumar , Pothana Pradeep , Kuppan Chandrasekhar 
Published: August 2022

Background:
1,2,3–Triazolyl–tetrazoles have received substantial attention because of its unique bioisosteric properties and extraordinarily broad spectrum of biological activity, making them interesting for the drug design and synthesis of delightful class of widely investigated heterocyclic compounds. To address major health concerns, it is consequently important to devote ongoing effort for the identification and development of New Chemical Entities (NCEs) as possible anticancer medicines.

Methods:
We began our initial investigation of the reaction between 5-(azidomethyl)-1H-pyrrolo[2,3-b]pyridine, 1-phenylsubstituted-5-(prop-2-yn-1-ylthio)-1H-tetrazole under click chemistry to gave the corresponding triazole precursors and screened for their cytotoxicity reported by variations in therapeutic actions of parent molecule. All of the prepared scaffolds were characterised by proton, carbon resonance spectroscopy, IR, and mass spectral techniques.

Results:
When tested for in vitro antitumor activity that the prepared compounds 7e, 7h had a signiﬁcant anticancer activity against human adenocarcinoma Hs766T cell line with IC50 = 5.33, 4.92 μg/mL and Hs460 cell line with IC50 = 4.82, 6.15 μg/mL respectively. Final scaffolds 7f, 7h, 7j acquiring highest potential drug binding scores ΔG = –10.42, –8.80, –9.37 Kcal/, with amino acids residues Ala A:11 (2.195 A˚), Asp A:119 (1.991 A˚), Thr A:58 (1.890 A˚), Lys A:16 (1.253 A˚), Asp A:38 (2.013 A˚), Lys A:117 (2.046 A˚) respectively and processing Lipinski’s rule of five as good oral bioavailability agents.

Conclusion:
The molecular framework for the synthesis of novel azaindole 1,2,3–triazole scaffolds coupled to tetrazole core was discovered in our study and evaluation of anticancer activity.
Synthesis and Computational Study of Some New 1-(1H-indol-1- yl)ethanone Derivatives on COX-2 Enzyme and Evaluation of In-Vivo Analgesic and Anti-inflammatory Activity
Authors: Kumar Arvind , Kumar Deepika , Porwal Mayur , Mishra Arun Kumar 
Published: August 2022

Background:Indole and its derivatives play an important role in the synthesis of commercially relevant intermediate molecules required for the synthesis of a wide range of bioactive molecules.Aim:Exploration of the synthesis of novel nonsteroidal anti-inflammatory drugs, as well as their computational studies and pharmacological effects, was aimed as an important component of the present research.Objective:the objective of present work was to synthesize some novel 1-(1H-indol-1-yl)ethanone compounds, analyse their computational effects on the COX-2 enzyme and to test their in vivo analgesic and anti-inflammatory activity.Methods:The condensation of 4-(2-(1H-indol-1-yl)-2-oxoethoxy) benzaldehyde with substituted aniline in ethanol in the presence of a catalytic quantity of glacial acetic acid was performed, which yielded the new Indole derivatives. IR, NMR, mass spectroscopy and elemental analysis techniques were used to characterize the structures of new indole derivatives.:To estimate the drug-like candidate’s nature, a number of molecular attributes of these derivatives were computed. The synthesized derivatives were docked with a specific reference cyclooxygenase-2 (COX-2) enzyme. The physical similarity of the newly synthesized derivatives (D1-D8) and indomethacin (the reference drug) was determined by evaluating seven physicochemical features by a software.Results:Although the bioavailability/drug likeness was found to be in the standard range, the synthesized compounds exhibited close similarity with those of the reference drug, and subsequent optimization was necessary.Conclusion:The newly synthesized indole derivatives as COX-2 inhibitors were evaluated for their biological properties, which included anti-inflammatory and analgesic efficacyOther:D-7 (1-(1H-indol-1-yl)-2-(4-((4-nitrophenyl)imino)methyl)phenoxy)ethanone) was found to have the strongest anti-inflammatory and analgesic activity amongst the eight target compounds.
Anti-Toxoplasma gondii Activity of Curcumin: A Systematic Review of
Pre-clinical Studies
Authors: Cheraghipour Kourosh , Kalani Hamed , Shakib Pegah , Faridnia Roghiyeh , Ho Jeffery , Mardanshah Omid , Dolatshah Mehrdad , Sepahvand Asghar , Zivdaria Masoomeh 
Published: August 2022

Objective:
This study has focused on anti-Toxoplasma gondii activity of curcumin.

Methods:
In this systematic review, anti-parasitic activity of Curcuma longa on Toxoplasma gondii
was assessed. Therefore, several databases, including PubMed, Scopus, Web of Science, Embase and
Google Scholar, were searched from 2010 to 2020.

Results:
Of the 2200 papers retrieved between 2010 and 2020, six articles were reliable and were scrutinized.
In 2 in vitro studies, the most used strain was the RH strain of Toxoplasma gondii, whereas
among 4 in vivo studies, RH strain was found in 2 (50%) studies, Me49 strain in 1(25%) study, and RH
and Me49 strain in 1 (25%) study. In four in vivo studies, the most used animal model was BALB/c,
and Swiss albino was found in 1 study (25%) and Albino rats in 1 study (25%).

Conclusion:
Curcumin and nanoparticles formulated with curcumin are new and useful agents for the
treatment of parasitic diseases and reduction of drug resistance. The success of this therapeutic
approach stems from the specific action of Curcuma longa against parasites and pathogens.