bluuebunny/crossref_metadata_2025_split huggingface dataset:
Jingzhi Niuhuangjiedu Tablet Ameliorates Oral Mucositis via the AKT/NFκB/NLRP3 Signaling Pathway: A Network Pharmacology and Experimental Validation
Authors: Fan Chunlan , Wang Hongping , Yin Qiong , Li Pin , Ma Quantao , Lin Zhaozhou , Zhao Chen , Peng Ping , Wang Zijian , Lv Yingnan , Wang Zhibin 
Published: August 2024

Background:
Oral Mucositis (OM) is a common and highly symptomatic complication
of cancer therapy that affects patient function and quality of life. Jingzhi Niuhuangjiedu Tablet
(JNT) is derived from the famous Chinese herbal formulas Huanglian Jiedu and Fangfeng
Tongsheng decoctions, which have been widely used to treat heat toxin syndrome diseases, such as
acute pharyngitis, periodontitis, oral ulcers, and oral mucositis (OM), but the underlying mechanism
remains unclear.

Objectives:
This study validated the efficacy and explored the potential mechanisms of JNT in the
treatment of OM by integrating network pharmacological analyses and experimental verification.

Methods:
Network pharmacology and molecular docking techniques were used to predict the active
components, key targets, and potential mechanisms of action of JNT against OM.
The rat OM model was established by administering 5-Fluorouracil (5-FU) and acetic acid to the
rat oral mucosa. Lipopolysaccharide (LPS)-treated human gingival fibroblasts (HGFs) were used
as an inflammatory cell model. The GFP-NFκB HEK293T cell line was transfected to evaluate the
anti-NFκB activity of JNT.

Results:
A total of 236 Chinese herbal components and 201 corresponding targets were predicted
for OM treatment using JNT. Bicuculine, luteolin, wogonin, and naringenin were identified as the
important active compounds, while AKT1, ALB, IL6, MAPK3, and VEGFA were considered to be
the major targets. Molecular docking revealed that these active compounds exhibited strong binding
interactions with their targets. In vivo and in vitro experiments demonstrated that the anti-OM
effect of JNT might be closely related to AKT1, NFκB, caspase-1, and NLRP3, as well as biological
processes, such as inflammatory response and oxidative stress.

Conclusion:
Network pharmacological and experimental evidence indicates that JNT has a potential
therapeutic effect on OM by regulating the Akt/NFκB/NLRP3 pathway.
Caffeic Acid Reduces Ferroptosis to Dampen Inflammation of Keratinocytes in Psoriasis by Inhibiting EGR1-induced Transcription Activation of CHAC1
Authors: Li Yadi , Zhou Xiaoqian , Yang Zhusheng , Zhang Lichao , Yang Xiumin , Wei Aihua 
Published: August 2024

Background:
Ferroptosis of keratinocytes is closely associated with
amplification of skin inflammation in psoriasis. This study focuses on unlocking the role
of caffeic acid (CA), a polyphenol compound, in keratinocyte ferroptosis and
understanding the underlying mechanistic basis.

Methods:
The interaction between early growth response protein 1 (EGR1) and chac
glutathione specific γ‑glutamylcyclotransferase 1 (CHAC1) was predicted by
bioinformatics and validated via chromatin immunoprecipitation and dual-luciferase
reported assays. Their expressions in primary human epidermal keratinocytes were
altered by transfection of EGR1/CHAC1 overexpression or knockdown plasmids, and
then keratinocytes were followed by CA treatment and Erastin (ferroptosis inducer).
Keratinocyte viability was determined by CCK-8 assay, and the ferroptotic effect was
evaluated using colorimetric assay and flow cytometry. Proinflammatory cytokine
secretion by keratinocytes was detected via ELISA. Expressions of EGR1 and CHAC1
in keratinocytes were analyzed by qRT-PCR or Western blot.

Results:
Increased expressions of EGR1 and CHAC1 were detected in keratinocytes
with Erastin treatment. CA (100 μM) antagonized Erastin (10 μM)-induced decrease in
viability, increases in EGR1 and CHAC1 expressions, upregulation of MDA, ROS, and
Fe2+, downregulation of GSH and SOD, and secretion of proinflammatory cytokines
from keratinocytes. EGR1 overexpression potentiated Erastin-induced effects.
Moreover, EGR1 overexpression and CA mutually counteracted their effects on
Erastin-induced keratinocytes. EGR1 transcriptionally activated and positively
regulated CHAC1. The above Erastin-induced effects were neutralized by EGR1
knockdown but potentiated by CHAC1 overexpression. Moreover, EGR1 knockdown
and CHAC1 overexpression reversed each other's effects.

Conclusion:
CA reduces ferroptosis by inhibiting EGR1-induced activation of CHAC1
to dampen inflammation of keratinocytes in psoriasis. This study providing new
compounds and candidate targets for the clinical treatment of psoriasis.
Frequency of Human Leukocyte Antigen-B*57:01 Allele Carriers in People Living with HIV/AIDS in Türkiye
Authors: Yılmaz Erkan , Kurt Ahmet Furkan , Dogruel Mehtap , Sevgi Dilek Yıldız , Karaosmanoglu Hayat Kumbasar , Zerdali Esra , Meric Koc Meliha , Mete Bilgul , Tabak Fehmi 
Published: August 2024

Introduction:
Abacavir is among the first-line initial antiretroviral regimens for most
patients living with HIV/AIDS (PLWHA). Although well tolerated, it is associated with hypersensitivity
reaction (HSR), which is treatment-limiting and potentially life-threatening. HSR was
shown to be associated with the class I MHC allele, HLA-B*57:01. In this study, we aimed to
evaluate the prevalence of HLA-B*57:01 in PLWHA in Istanbul, Türkiye.

Material and Methods:
Five HIV treatment centers in Istanbul included all sequential treatment--
naïve, ≥ 18 years adult PLWHA, between December 2017- December 2021. Demographic, clinical,
and laboratory data were collected at baseline and during treatment. HLA-B* 57:01 genotyping
was determined with PCR-SSP.

Results:
Eight hundred sixty-seven PLWHA were included (male:91%, mean age 39.6±11.1
years). 1.6% of patients were found to be HLA-B*57:01 positive. Among HLA-B*57:01 positive
patients, 4 were initially given abacavir-containing treatment; they were switched to non-abacavir
treatment upon the allele found to be positive.

Conclusion:
Although previous studies reported the HLA-B*57:01 prevalence of PLWHA in
Türkiye as 3-3.6%, we have found the prevalence to be 1.6%. The current study includes higher
numbers of patients than the previous studies. Furthermore, patients from all over the country apply
to the centers in Istanbul; compared to the other studies, which involve patients limited to the
relevant regions, it can be assumed that the number in our cohort is more representative of the
country. In conclusion, the prevalence of the HLA-B*57:01 allele in PLWHA in this study is relatively
low. With evident benefit in preventing abacavir HSR, HLA-B*57:01 should be screened in
planning antiretroviral therapy.
Integration of Diabetes Mellitus and Hypertension on Major Cardiovascular Events: An Experience From a 15-year Follow-up Cohort Study in EMR
Authors: Sadeghi Masoumeh , Teimouri-Jervekani Zahra , Roohafza Hamidreza , Talaei Mohammad , Paknahad Mohammad Hossein , Dianatkhah Minoo , Boshtam Mansoureh , Sarrafzadegan Nizal 
Published: August 2024

Introduction:
Patients with hypertension and diabetes are more susceptible to cardiovascular
diseases (CVD) and mortality. This study aimed to evaluate the individual and combined
effects of hypertension and diabetes on cardiovascular events and mortality in a Middle
Eastern population-based cohort.

Methods:
Fifteen-year follow-up data were collected for 6323 adults aged 35 years and older
who were free from CVD at baseline. The subjects were categorized into different groups according
to hypertension and diabetes at baseline. Cox proportional hazards regression was implemented
to estimate hazard ratios (HRs) of hypertension and diabetes for cardiovascular events
(CVE), CVD mortality, and all-cause mortality. Population-attributable hazard fraction (PAHF)
was used to assess the proportion of hazards of CVE and mortality attributable to hypertension or
diabetes.

Results:
The incidence rates (95% CI) of CVE, CVE mortality, and all-cause mortality in the total
population were 13.77(12.84-14.77), 3.01(2.59-3.49), and 9.92(9.15-10.77) per 1000 persons
per year respectively. The HR of hypertension for CVE in the diabetic population was 1.98
(1.47-2.66) with a PAHF of 27.65(15.49-39.3). When the HRs and PAHF of diabetes were evaluated
in hypertensive patients, they were statistically significant for CVE, CVE mortality, and
all-cause mortality.

Conclusion:
Our study indicated that the joint effect of diabetes and hypertension is the dramatic
increased risk of CVE. A considerable fraction of the excess risk of CVE in patients with diabetes
was attributable to hypertension, on the other hand, diabetes was associated with a substantial
hazard fraction of CVE and mortality in hypertensive patients.
Synthesis and Evaluation of Antibacterial and Antifungal Activities In vitro and In silico of Novel Morpholinoalkoxychalcones
Authors: Phan Hoang Minh , Mai Tan Thanh , Don Thinh Nguyen Quang , Do Dat Thanh , Thai Khac Minh , Tran Thanh Dao , Truong Phuong , Huynh Phuong Nguyen Hoai 
Published: August 2024

Introduction:
Chalcone compounds exhibit diverse bioactivities, attracting significant
interest. Morpholine is a heterocycle commonly used in medicinal chemistry. It could enhance the
potency, pharmacokinetics, and bioactivities of its compounds.

Methods:
Adding morpholine into the chalcone scaffold could help create new compounds with
favorable bioactivities. In this study, a new parallel synthesis procedure has been developed. Using
this procedure, 18 novel morpholinoalkoxychalcones have been successfully synthesized. They had
chains with morpholine appended on ring A or ring B. All the synthesized compounds were
evaluated for the antibacterial and antifungal activities by agar diffusion method on 5 bacteria and 2
fungi strains.

Results:
The compounds with good inhibition were determined with respect to the MIC values by
the agar dilution method. Among the tested compounds, B.21 was found to be the best against E.
faecalis, with an MIC value of 0.6 mM. B.43 with an MIC value of 2.04 mM has displayed its potential
in inhibiting A. niger and C. albicans the best among other compounds.

Conclusion:
The in silico study has revealed two targets to align with the in vitro results. Longer
alkyl chains have enhanced the activity, along with the presence of OH, NH2, and halogen groups
on both rings A and B.
Exploring Thiophene Derivatives: Synthesis Strategies and Biological Significance
Authors: Mishra Isha , Sharma Vikram , Kumar Nitin , Krishna Gaurav , Sethi Vandana Arora , Mittal Ravi , Dhakad Prashant K. , Mishra Raghav 
Published: August 2024

Objectives:
Thiophene is one of the most important heterocyclic scaffolds with notable
pharmacological properties. Thiophene and its derivatives are of particular interest among sulphurcontaining
heterocycles because of their similarities to numerous natural and synthetic compounds
with identified potential. The purpose of this study is to extensively analyse the synthetic pathways
adopted for synthesising thiophene derivatives and investigate their various biological functions.

Methods:
A comprehensive review of the existing literature was conducted to collect data pertaining
to the methods that are employed for the synthesis of thiophene derivatives. A comprehensive
search was carried out through relevant databases, including work published in 2024. A variety of
synthesis procedures were identified and arranged, encompassing both traditional approaches like
the Gewald reaction and contemporary ones like microwave-assisted synthesis and green synthesis.
In addition, a comprehensive compilation of in vitro and in vivo studies was conducted to investigate
the biological effects of 50 distinct thiophene derivatives. The primary focus of the studies was
on various activities such as anti-cancer, anti-inflammatory, antiprotozoal, antibacterial, antioxidant,
and antiviral functions.

Results:
Diverse methodologies have been employed in the synthesis of thiophene derivatives,
encompassing both conventional and modern methods. Furthermore, the biological potential of
thiophene derivatives was investigated, demonstrating a broad range of actions. Key structural elements
necessary for biological activity were clarified by investigations of the structure-activity
relationship.

Conclusion:
The biological potential and flexible synthesis pathways of thiophene derivatives
make them attractive candidates for use in medicinal and pharmaceutical chemistry. Understanding
the different synthesis methods and biological actions of thiophene derivatives may assist rational
design and create novel treatments for a variety of conditions. The potential for these compounds to
be further explored and optimised is considerable for the next drug development initiatives.
Cyclanoline Reverses Cisplatin Resistance in Bladder Cancer Cells by Inhibiting the JAK2/STAT3 Pathway
Authors: Li Linjin , Li Chengpeng , Miao Feilong , Chen Wu , Kong Xianghui , Ye Ruxian , Wang Feng 
Published: August 2024

Background:
Cisplatin is a key therapeutic agent for bladder cancer, yet the emergence of cisplatin
resistance presents a significant clinical challenge.

Objective:
This study aims to investigate the potential and mechanisms of cyclanoline (Cyc) in overcoming cisplatin
resistance.

Methods:
Cisplatin-resistant T24 and BIU-87 cell models (T24/DR and BIU-87/DR) were established by increasing
gradual concentration. Western Blot (WB) assessed the phosphorylation of STAT3, JAK2, and JAK3.
T24/DR and BIU-87/DR cell lines were treated with selective STAT3 phosphorylation modulators, and cell viability
was evaluated by CCK-8. Cells were subjected to cisplatin, Cyc, or their combination. Immunofluorescence
(IHC) examined p-STAT3 expression. Protein and mRNA levels of apoptosis-related and cell cycle-related factors
were measured. Changes in proliferation, invasion, migration, apoptosis, and cell cycle were monitored. In
vivo, subcutaneous tumor transplantation models in nude mice were established, assessing tumor volume and
weight. Changes in bladder cancer tissues were observed through HE staining, and the p-STAT3 was assessed via
WB and IHC.

Results:
Cisplatin-resistant cell lines were successfully established, demonstrating increased phosphorylation of
STAT3, JAK2, and JAK3. Cisplatin or Cyc treatment decreased p-STAT3, inhibited invasion and migration, and
induced apoptosis and cell cycle arrest in the G0/G1 phase in vitro. In vivo, tumor growth was significantly suppressed,
with extensive tumor cell death. IHC and WB consistently showed a substantial downregulation of
STAT3 phosphorylation. These changes were more pronounced when cisplatin and Cyc were administered in
combination.

Conclusion:
Cyc reverses cisplatin resistance via JAK/STAT3 inhibition in bladder cancer, offering a potential
clinical strategy to enhance cisplatin efficacy in treating bladder cancer.
A Novel Combinatorial Regimen Using Sorafenib and Uttroside B, A US FDA-designated ‘Orphan Drug’, for the Treatment of Hepatocellular Carcinoma
Authors: Keerthana Chenicheri Kizhakkeveettil , Aiswarya Sreekumar U. , Rayginia Tennyson P. , Vijayan Yadu , James Shirly , Shifana Sadiq C. , Sundaram Sankar , Induja D.K. , Lankalapalli Ravi S. , Harikumar Kuzhuvelil B. , Anto Ruby John 
Published: August 2024

Introduction:
Sorafenib (Sor) is the first-line treatment option in clinics for treating advanced unresectable
hepatocellular carcinoma (HCC). However, acquired chemoresistance and adverse side effects associated
with Sor monotherapy limit its clinical benefits. We have previously reported the exceptional anti-HCC potential
of uttroside B (Utt-B), a furostanol saponin isolated in our lab from Solanum nigrum Linn. leaves. The current
study has evaluated the supremacy of a combinatorial regimen of Sor and Utt-B over Sor monotherapy.

Methods:
MTT assay was used for In vitro cytotoxicity studies. A clonogenic assay was conducted to assess the
anti-proliferative effect of the combination. Annexin V/PI staining, confocal microscopy, FACS cell cycle analysis,
and Western blotting experiments were performed to validate the pro-apoptotic potential of the combination
in HepG2 and Huh7 cell lines. Pharmacological safety evaluation was performed in Swiss albino mice.

Results:
Our results indicate that Utt-B augments Sor-induced cytotoxicity in HepG2 and Huh7 cells. The combination
inhibits the proliferation of liver cancer cells by inducing apoptosis through activation of the caspases 7
and 3, leading to PARP cleavage. Furthermore, the combination does not induce any acute toxicity in vivo, even
at a dose five times that of the effective therapeutic dose.

Conclusion:
Our results highlight the potential of Utt-B as an effective chemosensitizer, which can augment the
efficacy of Sor against HCC and circumvent Sor-induced toxic side effects. Moreover, this is the first and only
report to date on the chemosensitizing potential of Utt-B and the only report that demonstrates the therapeutic
efficacy and pharmacological safety of a novel combinatorial regimen involving Utt-B and Sor for combating
HCC.
Application of Nanoparticles in the Diagnosis and Treatment of Colorectal Cancer
Authors: Song Qiuyu , Zheng Yifeng , Zhong Guoqiang , Wang Shanping , He Chengcheng , Li Mingsong 
Published: August 2024

:
Colorectal cancer is a common malignant tumor with high morbidity and mortality rates, imposing a
huge burden on both patients and the healthcare system. Traditional treatments such as surgery, chemotherapy
and radiotherapy have limitations, so finding more effective diagnostic and therapeutic tools is critical to improving
the survival and quality of life of colorectal cancer patients. While current tumor targeting research mainly
focuses on exploring the function and mechanism of molecular targets and screening for excellent drug targets, it
is crucial to test the efficacy and mechanism of tumor cell therapy that targets these molecular targets. Selecting
the appropriate drug carrier is a key step in effectively targeting tumor cells. In recent years, nanoparticles have
gained significant interest as gene carriers in the field of colorectal cancer diagnosis and treatment due to their
low toxicity and high protective properties. Nanoparticles, synthesized from natural or polymeric materials, are
NM-sized particles that offer advantages such as low toxicity, slow release, and protection of target genes during
delivery. By modifying nanoparticles, they can be targeted towards specific cells for efficient and safe targeting
of tumor cells. Numerous studies have demonstrated the safety, efficiency, and specificity of nanoparticles in targeting
tumor cells, making them a promising gene carrier for experimental and clinical studies. This paper aims to review
the current application of nanoparticles in colorectal cancer diagnosis and treatment to provide insights for
targeted therapy for colorectal cancer while also highlighting future prospects for nanoparticle development.
Elucidating the Mechanism of Jisheng Shenqi Pills in the Treatment of Diabetic Kidney Disease: Network Pharmacology Combined with Experimental Verification
Authors: Ma Xiaoshu , Zhou Guangju 
Published: August 2024

Background:
While the annual incidence of diabetic kidney disease (DKD) has been
soaring, the exact mechanisms underlying its onset and progression remain partially understood.

Objective:
The present study delved into the underlying mechanisms of Jisheng Shenqi Pill (JSP)
in the treatment of DKD.

Methods:
The active constituents and prospective targets of JSP were identified from the Traditional
Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), while
DKD-associated disease targets were obtained from the GeneCards database. Subsequently, Gene
Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG)
pathway enrichment analyses were performed to assess the overlapping segment of drugs and disease
targets. Meanwhile, a component-target-pathway network was constructed to identify pivotal
components, targets, and pathways. Molecular docking and molecular dynamics simulation were
also carried out to validate the binding efficacy of the pivotal components with the targets. Finally,
animal experiments were conducted to corroborate the efficacy of the aforementioned targets
and pathways.

Results:
According to bioinformatics analysis, the primary targets included JUN, TNF, and BAX,
while the pivotal pathways involved were AGE/RAGE and PI3K/AKT signaling cascades. In vivo
experiments demonstrated that JSP effectively mitigated renal impairment in DKD by reducing renal
inflammation and apoptosis. This effect was presumably achieved by modulating the AGERAGE
axis and the PI3K/AKT signaling pathway.

Conclusion:
Our findings imply that JSP could ameliorate renal inflammation and apoptosis in
DKD mice by modulating the AGE/RAGE axis and the PI3K/AKT signaling pathway. These findings
provide valuable insights into traditional Chinese medicine-based treatments for DKD.
A Comparative Analysis of Norepinephrine with Midodrine/Octreotide in Patients with Hepatorenal Syndrome-acute Kidney Injury
Authors: Maghsudlou Maryam , Nourozi Alireza , Mehravar Fatemeh , Amirkhanlou Saeid 
Published: August 2024

Background
Hepatorenal Syndrome (HRS) is a severe complication of end-stage liver disease characterized by functional renal impairment. This study aimed to assess the efficacy of norepinephrine compared to midodrine/octreotide in managing patients diagnosed with hepatorenal syndrome type 1.

Materials and Methods
In this double-blind Randomized Clinical Trial, 50 patients with hepatorenal syndrome type 1 were randomly assigned to the norepinephrine and midodrine/octreotide groups. The norepinephrine group received an initial dose of 1 mg/h (up to a maximum of 4 mg/h) along with daily intravenous injections of 20% albumin (20-40 grams per day) throughout the study period. The control group received midodrine (maximum dose of 15 mg three times a day), octreotide (maximum dose of 200 micrograms intravenously three times a day), and 20 to 40 mg of 20% albumin daily. The primary efficacy measure was the percentage of patients achieving a complete response, defined by the restoration of serum creatinine levels to within 0.3 mg/dl of the baseline by the end of treatment.

Results
There was no significant difference in the rate of complete response between the norepinephrine group (7/25, 28%) and the midodrine/octreotide group (3/25, 12%) (p=0.15). The mortality rate was 10 (40%) in the norepinephrine group and 12 (48%) in the midodrine/octreotide group. Although the mortality rate was higher in the midodrine/octreotide group (12/25, 48%) compared to the norepinephrine group (10/25, 40%), this difference was not statistically significant (p=0.77).

Conclusion
The study findings suggest that the norepinephrine treatment regimen can be as effective as or more effective than the midodrine/octreotide regimen in treating hepatorenal syndrome in cirrhotic patients. Therefore, these two treatment regimens can be used interchangeably.

Clinical Trial Registration Number
IRCT20230228057568N1