bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Silico and In vitro Analysis of Phenolic Acids for Identification of
Potential DHFR Inhibitors as Antimicrobial and Anticancer Agents
Authors: Sehrawat Renu , Rathee Priyanka , Rathee Pooja , Khatkar Sarita , Küpeli Akkol Esra , Khatkar Anurag 
Published: August 2023

Background:
DHFR is an indispensable enzyme required for the survival of almost all prokaryotic
and eukaryotic cells, making it an attractive molecular target for drug design.

Objective:
In this study, a combined in silico and in vitro approach was utilized to screen out potential
anticancer and antimicrobial agents by using DHFR PDB ID 2W9S (for antimicrobial) and 1U72 (for
anticancer).

Methods:
Computational work was performed using Maestro Schrodinger Glide software. The DHFR
inhibitory activity of the selected compounds was assessed using the DHFR test kit (CS0340-Sigma-
Aldrich).

Results:
Exhaustive analysis of in-silico results revealed that some natural phenolic acids have a good
docking score when compared to standards, i.e., trimethoprim and methotrexate, and have astonishing
interactions with crucial amino acid residues available in the binding pocket of DHFR, such as Phe 92,
Asp 27, Ser 49, Asn 18, and Tyr 98. In particular, digallic acid and chlorogenic acid have amazing interactions
with docking scores of -9.9 kcal/mol and -9.6 kcal/mol, respectively, for the targeted protein
2W9S. Docking scores of -10.3 kcal/mol and -10.2 kcal/mol, respectively, for targeted protein 1U72.
The best hits were then tested in vitro to evaluate the DHFR inhibitory activity of the compounds.
DHFR inhibition activity results are in correlation with molecular docking results.

Conclusion:
In silico and in vitro results confirmed the good binding and inhibitory activity of some
phenolic acids to the modeled target proteins. Among all the studied natural phenolic acids, chlorogenic
acid, digallic acid, and rosmarinic acid appeared to be the most potential leads for future chemical
alteration. This study can provide significant speculative guidance for the design and development
of potent DHFR inhibitors in the future by using these compounds as leads.
DNA Methyltransferase 3A: A Significant Target for the Discovery of Inhibitors
as Potent Anticancer Drugs
Authors: Feng Qixun , Duan Honggao , Zhou Xinglong , Wang Yuning , Zhang Jinda , Zhang Haoge , Chen Guoliang , Bao Xuefei 
Published: August 2023

Abstract:
DNA methyltransferase (DNMT) is a conserved family of Cytosine methylases, which
plays a crucial role in the regulation of Epigenetics. They have been considered promising therapeutic
targets for cancer. Among the DNMT family, mutations in the DNMT3A subtype are particularly important
in hematologic malignancies. The development of specific DNMT3A subtype inhibitors to
validate the therapeutic potential of DNMT3A in certain diseases is a significant task. In this review,
we summarized the small molecule inhibitors of DNMT3A discovered in recent years and their inhibitory
activities, and classified them based on their inhibitory mechanisms.
A New Hope in Alzheimer's Disease Psychosis: Pimavanserin
Authors: Kurhan Faruk , Akın Mustafa 
Published: August 2023

Abstract:
Alzheimer's disease (AD) ranks first among the causes of dementia worldwide. AD can
develop a psychotic manifest at a significant rate. AD prognosis worsens by added psychosis clinic.
There is no treatment approved by the United States Food and Drug Administration (FDA)
among antipsychotics for Alzheimer’s disease Psychosis (ADP). However, pimavanserine, an atypical
antipsychotic, has been approved by the FDA for Parkinson's psychosis. It is predicted that pimavanserin,
a new antipsychotic, will fill an important gap in this area. In clinical trials, it appears
to be effective in the treatment of delusions and hallucinations at psychosis in both Parkinson's and
AD. In this systematic review, we evaluated the analysis of current literature data on pimavanserin
used in ADP. We searched the existing literature on clinical studies on pimavanserin therapy used
in ADP. Data were determined by systematically searching PubMed, MEDLINE, EMBASE, and
Google Scholar until December 2022. A total of 35 citations were found and uploaded on the Mendeley
program. Abstracts and full texts of literature data were examined. Pimavanserin was observed,
and satisfactory results were obtained in treating ADP. Pimavanserin has a unique mechanism
of action. Pimavanserin, an atypical antipsychotic drug, has a low affinity for 5-HT2C receptors
and has selective 5-HT2A reverse agonist/antagonist action. Pimavanserin has no clinically significant
affinity for dopaminergic, histaminergic, muscarinic or adrenergic receptors. This agent
may also achieve significant positive results in resistant psychosis treatments.
A Comprehensive Review on Current Treatments and Challenges
Involved in the Treatment of Ovarian Cancer
Authors: Saman Saika , Srivastava Nimisha , Yasir Mohd , Chauhan Iti 
Published: August 2023

Abstract:
Ovarian cancer (OC) is the second most common gynaecological malignancy. It typically
affects females over the age of 50, and since 75% of cases are only discovered at stage III or IV,
this is a sign of a poor diagnosis. Despite intraperitoneal chemotherapy's chemosensitivity, most patients
relapse and face death. Early detection is difficult, but treatment is also difficult due to the
route of administration, resistance to therapy with recurrence, and the need for precise cancer targeting
to minimize cytotoxicity and adverse effects.

:
On the other hand, undergoing debulking surgery becomes challenging, and therapy with many chemotherapeutic
medications has manifested resistance, a condition known as multidrug resistance
(MDR). Although there are other therapeutic options for ovarian cancer, this article solely focuses
on co-delivery techniques, which work via diverse pathways to overcome cancer cell resistance.
Different pathways contribute to MDR development in ovarian cancer; however, usually, pump
and non-pump mechanisms are involved. Striking cancerous cells from several angles is important
to defeat MDR. Nanocarriers are known to bypass the drug efflux pump found on cellular membranes
to hit the pump mechanism.

:
Nanocarriers aid in the treatment of ovarian cancer by enhancing the delivery of chemotherapeutic
drugs to the tumour sites through passive or active targeting, thereby reducing unfavorable side effects
on the healthy tissues. Additionally, the enhanced permeability and retention (EPR) mechanism
boosts the bioavailability of the tumour site. To address the shortcomings of conventional delivery,
the current review attempts to explain the current conventional treatment with special reference
to passively and actively targeted drug delivery systems (DDSs) towards specific receptors developed
to treat ovarian cancer. In conclusion, tailored nanocarriers would optimize medication delivery
into the intracellular compartment before optimizing intra-tumour distribution. Other novel
treatment possibilities for ovarian cancer include tumour vaccines, gene therapy, targeting epigenetic
alteration, and biologically targeted compounds. These characteristics might enhance the therapeutic
efficacy.
Shugan Jiangzhi Decoction Alleviates Nonalcoholic Fatty Liver Disease (NAFLD) via Regulating AMPK/PPAR Signaling Pathway
Authors: Chen Lijuan , Li Wen , Fu Yanli , Lei Yuhe , Xie Wenjian , Rong Suihua , Li Ning , Zhang Miaomiao , He Jiayi , Chen Yanfen , Wu Dinghong 
Published: August 2023

Background:
Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disease.
Shugan Jiangzhi Decoction (SJD), a traditional Chinese medicine (TCM) formula which consists of six Chinese
herbs, has been used for treating hyperlipidemia, obesity, and fatty liver in Guangdong Provincial Hospital of
Traditional Chinese Medicine for over twenty years.

Objective:
This study aims to elucidate the chemical basis and the molecular mechanism of SJD against NAFLD.

Methods:
The main components of SJD were determined by High Performance Liquid Chromatography (HPLC).
Then the high-fat diet (HFD)-induced NAFLD rat model was established. After treatment with different doses of
SJD, the body weight of rats was measured weekly. On the last day of the experiments, the hepatic morphology,
histopathology changes, and the serum lipid levels were detected. Then techniques of network pharmacology
were employed to predict the anti-NAFLD mechanism of SJD. At last, the expression levels of proteins were
measured by western blot to verify the mechanism.

Results:
Nine chemical constituents of SJD were identified from HPLC fingerprint spectrum. For the in vivo experiment,
NAFLD rat model was constructed successfully by feeding high-fat diet (HFD) for 8 weeks. The following
treatment with SJD for 6 weeks decreased the fatty droplet accumulation in the liver obviously. Meanwhile,
the serum level of high-density lipoprotein cholesterol (HDL-c) was increased, while the levels of lowdensity
lipoprotein cholesterol (LDL-c), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)
were decreased after SJD treatment (p < 0.05). The results of network pharmacology indicated that SJD might
improve NAFLD via regulating the AMPK/PPAR signaling pathway. Then, the western blot assay confirmed that
SJD activated the AMPK/PPAR signaling pathway in the liver of rats.

Conclusion:
SJD improves HFD-induced NAFLD in rats via AMPK/PPAR signaling pathway. Thus, our
study suggests that SJD can serve as a therapeutic agent for the prevention and treatment of NAFLD.
The Gap in Knowledge about Tapering Targeted Therapy being used as
Monotherapy in Rheumatoid Arthritis: A Systematic Review
Authors: Meng Charis F. , Rajesh Diviya A. , Jannat-Khat Deanna P. , Jivanelli Bridget , Bykerk Vivian 
Published: August 2023

Background:
Up to 30% of patients with RA are being treated with biologic (b)-disease
modifying anti-rheumatic drugs (DMARDs) as monotherapy. Monotherapy with Interleukin (IL)-6
inhibitors(i) and Janus-kinase (JAK)-i has been shown to be effective. Whether patients can taper
targeted therapy (bDMARDs and JAK-i) used as monotherapy (targeted monotherapy) is unknown.

Objective:
To determine the feasibility of tapering of targeted monotherapy in patients with controlled
RA.

Methods:
We conducted a literature search in Medline, Embase and Cochrane Library for prospective
studies reporting remission outcomes after tapering targeted monotherapy in RA patients, from
1/2014 - 8 /2021.

Results:
5 randomized studies which met our inclusion criteria, evaluating tapering of monotherapy
with tumor necrosis factor-inhibitors, tocilizumab, abatacept and baricitinib in RA. Studies were
heterogeneous. Three trials studied early RA. Three studies gradually tapered therapy, including 1
dose reduction study. Three studies tapered both biological and conventional-synthetic (cs)-DMARDs.
No study compared stopping targeted monotherapy to continuing it. Remission rates
were low 14-28% across all studies that stopped targeted monotherapy. The highest remission rate
of 72% was reported by the dose reduction study. Trials that studied early RA reported remission
rates after tapering ranging 27-72%. Trials tapering therapy in established RA reported rates of remission
from 14-20%.

Conclusion:
There is a crucial gap in published literature to inform on tapering targeted monotherapy
in patients with RA. Stopping targeted monotherapy is unlikely to maintain disease control in
RA. Dose reduction strategies and early treatment of disease may be associated with more successful
tapering, and warrant future study.
Current State and Future Perspective of Diabetic Wound Healing
Treatment: Present Evidence from Clinical Trials
Authors: Dwivedi Jyotsana , Sachan Pranjal , Wal Pranay , Wal Ankita , Rai A. K. 
Published: August 2023

Abstract:
Diabetes is a chronic metabolic condition that is becoming more common and is characterised by sustained hyperglycaemia and long-term health effects. Diabetes-related wounds often heal slowly and are more susceptible to infection because of hyperglycaemia in the wound beds. The diabetic lesion becomes harder to heal after planktonic bacterial cells form biofilms. A potential approach is the creation of hydrogels with many functions. High priority is given to a variety of processes, such as antimicrobial, pro-angiogenesis, and general pro-healing. Diabetes problems include diabetic amputations or chronic wounds (DM). Chronic diabetes wounds that do not heal are often caused by low oxygen levels, increased reactive oxygen species, and impaired vascularization. Several types of hydrogels have been developed to get rid of contamination by pathogens; these hydrogels help to clean up the infection, reduce wound inflammation, and avoid necrosis. This review paper will focus on the most recent improvements and breakthroughs in antibacterial hydrogels for treating chronic wounds in people with diabetes. Prominent and significant side effects of diabetes mellitus include foot ulcers. Antioxidants, along with oxidative stress, are essential to promote the healing of diabetic wounds. Some of the problems that can come from a foot ulcer are neuropathic diabetes, ischemia, infection, inadequate glucose control, poor nutrition, also very high morbidity. Given the worrying rise in diabetes and, by extension, diabetic wounds, future treatments must focus on the rapid healing of diabetic wounds.
Severe and Prolonged Thrombocytopenia Following Heparin and Apixaban
Use: A Case Report and Literature Review
Authors: Salimi Mehdi , Shahbazi Foroud 
Published: August 2023

Abstract:
Drug-induced thrombocytopenia can occur in hospitalized patients and complicate their antithrombotic
treatment. Several medications can associate thrombocytopenia with immune and nonimmune
mechanisms. Thrombocytopenia can occur at any time from a few hours to months after a
new medication initiation. In this study, we have described the case of a female patient with acute-onchronic
kidney injury following a non-steroidal anti-inflammatory agent use, who developed catheterrelated
thrombosis and was treated with heparin without any complication for 5 days. She was discharged
after 5 days and prescribed to use apixaban 2.5 mg twice daily. However, she was readmitted
after 24 hours with fatigue, petechiae, and severe thrombocytopenia (7000/mm3). The workup was
negative for other reasons of thrombocytopenia. With a possible diagnosis of drug-related thrombocytopenia,
apixaban was discontinued. Following the treatment with the intravenous immunoglobulin,
her platelet counts increased and stabilized around 40-50,000/mm3. Anticoagulation was thus continued
with adjusted doses of rivaroxaban (10-15 mg/day). 17 days after apixaban discontinuation and
treatment with prednisolone, her platelet count increased to 108,000/mm3. With reference to this case,
a brief review on refractory heparin-induced thrombocytopenia and the association of direct oral anticoagulants
with thrombocytopenia is presented.
Juglone Mediates Inflammatory Bowel Disease Through Inhibition of
TLR-4/NF KappaB Pathway in Acetic Acid-induced Colitis in Rats
Authors: Alizadeh Nobakht Neda Agha , Lashgari Naser-Aldin , Momeni Roudsari Nazanin , Niknejad Amirhossein , Khayatan Danial , Tavakoli Saeed , Abdollahi Ali Reza , Esmaealzadeh Niusha , Momtaz Saeideh , Abdolghaffari Amir Hossein 
Published: August 2023

Background:
Juglone is a phenolic bioactive compound with antimicrobial, anti
tumour, antioxidant, and anti inflammatory characteristics. Given its anti inflammatory and an-tioxidant effects, it was selected for evaluation in the inflammatory bowel diseases (IBD) model.

Objective:
The current study was performed to evaluate the therapeutic impacts of the juglone in acetic acid induced colitis in male Wistar rats.

Methods:
Juglone was extracted from Pterocarya fraxinifolia via maceration method. Colitis was induced in 36 male Wistar rats (n = 6), except in the sham group, 1 ml of acetic acid 4% was administered intrarectally. Twenty four hours after induction of colitis, in 3 groups, juglone was administered orally (gavage) at 3 doses of 50, 100, and 150 mg/kg for 2 successive days (once a day). Other groups included the control group (only treated with acetic acid), sham group (nor-mal saline), and standard group (Dexamethasone). To evaluate the inflammation sites, macro-scopic and microscopic markers were assessed. The mRNA expression of interleukin ( 1β, and tumor necrosis factor alpha ( α were assessed by real time PCR, while myeloperoxidase (MPO) was measured spectrophotometrically. ELISA assay kits were used to determine the colonic levels of SOD, ROS, NF κB, and TLR 4.

Results:
Results: Macroscopic and microscopic assessments revealed that juglone significantly decreased
colonic tissue damage and inflammation at 150 mg/kg. Juglone at 100, 150 mg/kg significantly
decreased the TNF-α, MPO, and TLR-4 levels, as well as the SOD activity. All juglone-treated
groups reduced the NF-κB levels compared to the control group (p < 0.001). The compound decreased
the IL-1β, and ROS levels at the concentration of 150 mg/kg. Juglone attenuated colitis
symptoms, reduced inflammation cytokines, declined neutrophil infiltration, and suppressed IL-
1β and TNF-α expressions in acetic acid-induced colitis rats. It may be proposed that juglone
improved colitis in animal model through suppression of inflammatory parameters and downregulation
of the NF-κB-TLR-4 pathway.

Conclusion:
Juglone exhibited anti inflammatory and antioxidant effects in the experimental colitis model and could be a therapeutic candidate for IBD. Juglone should be a subject for fur-ther animal and clinical trials in IBD models and for safety concerns.
Combination Therapy: A New Tool for the Management of Obesity
Authors: Prabhakar Pranav Kumar 
Published: August 2023

Abstract:
Obesity is a chronic lifestyle issue with devastating results. Behavioral changes are one
of the initial lines of management strategies for obesity, but they are not very efficient management
strategies. Many people also use surgical intervention to maintain a healthy weight, now
considered to be the most common and effective obesity management. Chemically synthesized
medicines fill the gap between lifestyle interventions and minimally invasive surgical management
of obesity. The most common issue associated with monotherapy without side effects is its moderate
effectiveness and higher dose requirement. Combination therapy is already used for many serious
and complicated disease treatments and management and has shown efficacy as well. Generally,
we use two or more medicines with different mechanisms of action for a better effect. The
commonly used combination therapy for obesity management includes low-dose phentermine and
prolonged and slow-releasing mechanism topiramate; naltrexone, and bupropion. Phentermine
with inhibitors of Na-glucose cotransporter-2 or glucagon-like peptide-1 (GLP-1) agonists with
gastric hormone or Na-glucose cotransporter-2 are two more viable combo therapy. This combination
strategy aims to achieve success in bariatric surgery and the scientific community is working
in this direction.
Benefits of Mediterranean and Japanese Diets among Nurses: A Scoping Literature Review
Authors: Vitale Elsa 
Published: August 2023

Introduction:
The present study aimed at all the benefits induced by taking the Mediterranean or Japanese diet among nurses and whether any beneficial differences in intakes between the two diets were considered.

Methods:
The author searched PubMed and Embase databases for medical subheadings terms and free full text referring to “Diet,” “Mediterranean,” “Japanese,” and “Nurses” before 31st December 2022.

Results:
A total of 14 studies were included in this scoping review, which better underlined all the benefits implicated in the Mediterranean or Japanese diets assumption and also if there were any differences between the two diets. These eating behaviors were exclusively investigated among nurses.

Conclusion:
The nursing profession has always been considered the most stressful healthcare activity. However, some important concerns in the regular lifestyle, such as eating and physical activity, might help to live better.
Intelligent Spraying Robot: Current Status and Future Perspectives from the Perspective of China
Authors: Yao Rongzheng , Xie Baocheng 
Published: August 2023

Background:
Spraying, as an important part of industrial production, is a labor-intensive industry. Manual spraying is greatly influenced by the personal factors of the operators. Furthermore, there are some problems in this method, such as substandard environmental protection and unstable spraying quality. However, intelligent spraying robots can effectively improve the efficiency of spraying, safety, environmental protection, flexible production, and high-quality spraying and reduce labor requirements. Therefore, the development trend of intelligent spraying robots has received increasing attention.

Objective:
In order to solve the problem that manual spraying is harmful to workers and is inefficient, the joint-type and non-joint-type intelligent spraying robots are constantly improving.

Methods:
The patents of intelligent spraying robots are summarized. The structural characteristics, advantages, and disadvantages of various intelligent spraying robots are introduced.

Results:
By investigating the patents of intelligent spraying robots, the main problems, such as poor manufacturing ability of high-end parts and insufficient software research and development, are summarized. In addition, the development trend of intelligent spraying robots is also discussed.

Conclusion:
The analysis shows that the intelligent spraying robot is an efficient and safe pioneering work. Compared with manual spraying, it has a very broad application prospect in various industrial spraying and is helpful to the development of the manufacturing industry.
Linguistic, Metalinguistic and Psychiatric Characteristics of
Children with Speech Sound Disorder
Authors: Amidfar Meysam 
Published: August 2023

Abstract:
Comparing the linguistic and metalinguistic profiles in common developmental
speech and language disorders is important in advancing our understanding of their clinical
symptoms, as well as potentially informing the conceptual basis of novel interventions. The
purpose of the present review article is summarizing linguistic, metalinguistic and psychiatric
characteristics of children with speech sound disorder (SSD). Clinically and theoretically, it is
important that we can understand different error pattern uses among children with SSD only
and children with co-occurring SSD and language impairment (LI). Identifying differences in
error pattern use will help to discovering the underlying causes of the different types of patterns.
In comparison with children with SSD, children with co-occurring SSD and LI use certain
patterns more frequently that suggest more global linguistic deficits. The early identification
of children who are at risk for development of co-occurring SSD and LI as well as later
literacy problems needs to distinguish these patterns. Identification of speech error patterns and
their underlying cognitive-linguistic processing deficits will contribute to diagnosis of children
at risk of co-occurring SSD and LI and reading problems. Mounting studies have reported that
children with SSD, with and without language impairment have differences in phonological
processing, literacy skills, and speech production patterns. Children with both speech sound
and language disorders are likely to have more severe literacy problems than those with isolated
speech sound disorders. In addition, this paper focuses on the comorbidity between psychiatric
disorders specially attention deficit/hyperactivity disorder (ADHD) symptoms and SSD.