bluuebunny/crossref_metadata_2025 huggingface dataset:
Rutenyum Mediyatör Kompleksi Temelli Galaktoz Biyosensörü Geliştirilmesi
Authors: CANBAY Erhan , KUNDAKÇI Şevval , YILDIZ Ezginur , ÇELİK CANBAY Zeynep , DOĞAN Serçin , AKYILMAZ Erol
Published: November 2023

Galaktoz seviyesinin ölçümü, galaktozemi ve galaktoz intoleransı açısından klinik önem taşır. Özellikle yenidoğanlarda hemen tespit edilmemesi ölümcül sonuçlar doğurabilir. Teşhis konduktan sonra da galaktozun diyetten çıkarılması gerekir. Dolayısıyla hem kan hem de diyette özellikle süt ve süt ürünlerinde galaktozun tayini büyük önem taşır. Literatür verilerinde galaktoz tayini için geliştirilen yöntemler spektrofotometre, kromatografi, kütle spektrometresi gibi ön işlem ve pahalı ekipman gerektiren, zaman alıcı ve nispeten yavaş yöntemlerdir. Bu çalışmanın amacını da galaktoz tayini için hızlı, spesifik, ucuz elektrokimyasal bir biyosensör sistemi geliştirilmesi oluşturmaktadır. Biyokomponent olarak Galaktoz Oksidaz (GaOX) enzimi kullanılan bu çalışmada, çalışma elektrodu olarak Rutenyum mediyatör kompleksi içeren karbon pasta elektrot kullanılmıştır. GaOX enzimi pasta yapısı içerisinde immobilize edilmiştir. Çalışmanın özgünlüğünü pasta yapısı içerisinde kullanılan Rutenyum mediyatör sisteminin kullanılması oluşturmaktadır. Elektrot yapım aşamaları döngüsel voltammetri (CV) yöntemiyle karakterize edilirken, optimizasyon ve karakterizasyon çalışmaları 0&0.9 V arası DP, ve 0.5 V’ta amperometrik ölçümler yoluyla gerçekleştirilmiştir. Çalışmalarda ayrıca çalışma tamponu içerisinde 1 mM p-benzokinon mediyatör sistemi kullanılmıştır.Optimizasyon çalışmaları sonu optimum pH 6,5, optimum sıcaklık ise 30 oC olarak bulunmuştur. Geliştirilen biyosensörün doğrusal tayin aralığı 0.05 – 1 mM arası bulunurken, tekrarlanabilirliği 0.25 mM galaktoz için ortalama 0.24 mM, standart sapma ± 0.021 ve varyasyon katsayısı (%VK) %8,3 olarak bulunmuştur. Girişim etkisi denemesinde herhangi bir girişim gözlenmemiştir. Örnek denemesi liyofilize serum ve laktozsuz süt örneklerinde yapılmış ve % geri elde hesaplanmıştır. Bu projede kullanılan Rutenyum mediyatör kompleksinin biyosensör yapımında kullanılmasına literatürde çok az rastlanılmış olmakla birlikte bu çalışmayla ilk defa bir galaktoz biyosensöründe ve ilk defa bir karbon pasta elektrotla kullanımı gerçekleştirilmiştir.
Antifungal Activity of Extracts From the Ferulago Pauciradiata in Vitro Against Botrytis Cinerea Pers
Authors: KARAKUŞ Sinem , SUYURDU Tuba Nur , KÖKSAL Ekrem , ALP Cemalettin
Published: November 2023

This is the first study to reveal the antifungal properties of Ferulago pauciradiata plant. In this context investigated the effects of methanol (FPM), ethanol (FPE), hexane (FPH) and water (FPW) extracts of the F. pauciradiata plant on the prevention of losses caused by gray mold (Botrytis cinerea Pers) in vitro. The effects of FPM, FPE, and FPH 10, 25, 50, 100, 300, 500, 1000, and 2000 µL doses were determined by mycelium growth, germ tube elongation, and spore germination in vitro. The water extract didn’t show antifungal activity against B. cinerea. Compared to the control, both FPM and FPH caused 100% inhibition at the dose of 2000 µL by suppressing mycelial growth due to dose increases, while FPE had a 97.3% effect on the same parameter at the dose of 2000 µL. While there was no elongation at the 2000 µL dose of FPM and FPH, there was an elongation of 8.4 µm at the same dose of FPM. In spore germination, 0% germination was observed in FPM and FPH 2000 µL dose, while 17.5% germination was observed in FPE. These results show that F. pauciradiata extracts, which are of biological origin and are not environmentally toxic, are a good alternative for use in the control of B. cinerea.
Bazı Orkide Türlerinde Ekim Öncesi Tohum Uygulamaları ve Bu Uygulamaların Tohum Çimlenme ve Gelişmesine Olan Etkisi
Authors: ÖZKOÇ İbrahim , BİLGİ Mustafa , GÜRKANLI Cem Tolga , MUSTAFA Luau
Published: November 2023

Bitkilerin gelişimi söz konusu olduğunda öncelikle ilk aşama bitki tohumunun sağlıklı bir şekilde çimlenmesidir. Bu durumun gerçekleşmesi orkideler söz konusu olduğunda diğer bitki türlerine göre daha zor olabilmektedir. Bu çalışmamızda elimizde bulunan orkide tohumlarının in-vitro olarak çimlenmesi gözlemlenmiştir. Sıcaklık, kuraklık, Ph gibi abiyotik faktörler, tohum çimlenmesine karşı stres oluşturabilmektedir ve tohumun çimlenmesini engelleyici etkiye sahip olmaktadır. Bu durumu engelleyebilmek için tohumların bazı yöntemlerle biyolojik ajanlarla kaplanması sağlanmıştır. Bu çalışmamızda, daha öneceki çalışmalarımızda izole ettiğimiz endofitik bakteri ve fungal izolatlar kullanılarak, laboratuvar ortamında tohumlar biyopriming uygulamalara tabii tutularak kaplanmış ve orkide tohumlarının çimlenmelerine olumlu bir etkisi olup olmadığı gözlemlenmiştir. Yapılan değerlendirmede özellikle hem endofitik fungal ve bakteri örneklerini içeren karışımların en etkili işlemler olduğu görülmüştür. Bu çalışma orkidelerde hem fungal hem de bakteriyel probiyotik denemesinin ilk örneğini oluşturmaktadır.
Ekmeklik Buğday (Triticum aestivum L.) Genotiplerinin Dane Verimi ve Bazı Önemli Kalite Özellikleri için Trakya Bölgesinde Bulunan Farklı Çevrelerde Testlenmesi
Authors: GÖKDERE Halil İbrahim , YILMAZ Ali Baran , TEKİN Mehmet , YEKEN Mehmet Zahit , ÇİFTÇİ Vahdettin
Published: November 2023

Bu çalışma, toplamda 27 çeşit ve çeşit adaylarının dane verimi ve bazı önemli kalite özellikleri bakımından genotip x çevre etkileşimi temel bileşen, GGE biplot ve AMMI analizleri değerlendirmek amacıyla Trakya bölgesini temsil eden dört farklı çevrede 2020-2021 sezonunda yürütülmüştür. Denemeler tesadüf blokları deneme desenine göre dört tekerrürlü yürütülmüş olup ve tarımsal ve kalite özelliklerinden başaklanma gün sayısı, bitki boyu, dane verimi, bin dane ağırlığı, hektolitre ağırlığı, dane sertliği, protein oranı, Zeleny sedimantasyon, Alveograf enerji değeri, yaş gluten oranı ve gluten indeksi çalışma kapsamında incelenmiştir. Çalışmada, dane veriminde en yüksek varyasyon Tekirdağ çevresinde belirlenmiş olup en yüksek verim ise Edirne çevresinde belirlenmiştir. GGE biplot analizine göre iki farklı mega çevre oluşmuş ve iki temel bileşen toplamda %89.97 genotip x çevre ilişkisini açıklamıştır. AMMI temelli varyans analizi sonucunda ise genotip, çevre, tekerrrür ve genotip x çevre interaksiyonu bakımından istatistiki olarak önemli etkiler tespit edilmiştir. En stabil genotipler ise Ez11 ve Rumeli olarak belirlenirken LG Arnova çeşidi dört çevrede de öne çıkan dört genotipten biri olmuştur. Korelasyon analizine sonucunda kalite özellikleri arasında istatistiki olarak önemli (p
Agreement of bioimpedance analysis and ultrasound scanning for fat mass, fat free mass and body fat percentage evaluation in the group of adult women
Authors: Bondareva Elvira , Parfenteva Olga , Vasileva Aleksandra , Kulemin Nikolay , Gadzhiakhmedova Aida , Kovaleva Olga , Khromov-Borisov Nikita
Published: November 2023

The study aims to perform an agreement analysis of bioimpedance (BIA) results obtained using АВС-02 “Medas” (Russia) and ultrasound scanning (US) using BodyMetrixTM (USA) for fat mass, fat free mass and body fat percentage in the group of females from Moscow. The study was performed with 180 female subjects 18-67 years of age. The agreement analysis conducted in the whole sample revealed a low level of agreement in estimating body fat percentage (CCC = 0.70 0.76 0.81) and fat free mass (CCC = 0.86 0.89 0.91), but agreement can be described as medium in estimating fat mass (CCC = 0.90 0.92 0.94). Then we adjusted the prediction equations and the agreement analysis was conducted again. Adjusted prediction equations improved the level of agreement to medium when estimating body fat percentage and fat free mass. Thus, the proposed equations can be used for the translation of body composition results obtained by US into the BIA data.
MicroRNA3650 Promotes Gastric Cancer Proliferation and Migration
through the PTEN/PI3K-AKT-mTOR and Hippo Pathways
Authors: Yang Xiansheng , Wen Juncai , He Qingjun , Wang Shuoshan , Ruan Qiang , Liao Quanxing , He Jinfu , Fang Shuxian , Liu Chang , Tang Hongsheng
Published: November 2023

Background::

Gastric cancer (GC) is a malignant tumor with seriously poor outcomes.
Studies have shown that microRNAs (miRNAs) play an omnifarious regulatory effect in GC.
However, the role of miR-3650 in the progression of GC is not well known.

Methods::

In this study, miR-3650 expression and its clinical significance were determined using
clinical specimens. The biological functions of miR-3650 were determined in gastric cancer cell
lines through CCK-8, cell scratch, and transwell experiments. Bioinformatics predictions, combined
with Western blot experiments, were employed to explore its downstream molecular targets.

Results::

We observed that miR-3650 was overexpressed in GC specimens and most cell lines, i.e.,
77.8% (MKN28, SNU1, AGS, MKN45, N87, BGC823 and SGC7901). The overexpression correlated
with advanced T-stage, N-stage, M-stage, and TNM-stage. Furthermore, miR-3650 promoted
the proliferation and migration of gastric cancer cells, and its overexpression promoted the
PI3K-AKT-mTOR pathway and inhibited the PTEN and hippo pathways. The potassium ion signaling
pathway was also involved in the biological process of miR-3650 promoting cancer.

Conclusion::

Therefore, we concluded that miR-3650/PTEN/PI3K-AKT-mTOR and
miR-3650/hippo pathways are vital in the progression of GC and serve as novel targets for GC
therapy.
Bioinformatics-based Analysis and Verification of Chromatin Regulators and the Mechanism of Immune Infiltration Associated with Myocardial Infarction
Authors: Zhao Huanyi , Tang Na , Xu Liang , Li Junlong , Pi Jianbin , Chu Qingmin
Published: November 2023

Background:

Recent studies have shown that dysfunction in chromatin regulators
(CRs) may be an important mechanism of myocardial infarction (MI). They are thus expected
to become a new target in the diagnosis and treatment of MI. However, the diagnostic value of
CRs in MI and the mechanisms are not clear.

Methods:

CRs-related differentially expressed genes (DEGs) were screened between healthy
controls and patients with MI via GSE48060, GSE60993, and GSE66360 datasets. DEGs were
further analyzed for enrichment analysis. Hub genes were screened by least absolute shrinkage
and selection operator (LASSO) regression and weighted gene co-expression network analysis
(WGCNA). GSE61144 datasets were further used to validate hub genes. RT-qPCR examined
peripheral blood mononuclear cells (PBMCs) to verify expressions of hub genes. In addition, a
correlation between hub genes and immune cell infiltration was identified by CIBERSORT
and single-sample gene set enrichment analysis (ssGSEA). Finally, we constructed a diagnostic
nomogram and ceRNA network and found possible therapeutic medicines which were
based on hub genes.

Results:

Firstly, 16 CR-related DEGs were identified. Next, Dual-specificity phosphatase 1
(DUSP1), growth arrest and DNA damage-inducible 45 (GADD45A), and transcriptional regulator
Jun dimerization protein 2 (JDP2) were selected as hub genes by LASSO and WGCNA.
Receiver operating characteristic curves in the training and test data sets verified the reliability
of hub genes. Results of RT-qPCR confirmed the upregulation of hub genes in MI. Subsequently,
the immune infiltration analysis indicated that DUSP1, GADD45A, and JDP2 were
correlated with plasmacytoid dendritic cells, natural killer cells, eosinophils, effector memory
CD4 T cells, central memory CD4 T cells, activated dendritic cells, and activated CD8 T cells.
Furthermore, a nomogram that included DUSP1, GADD45A, and JDP2 was created. The calibration
curve, decision curve analysis, and the clinical impact curve indicated that the nomogram
could predict the occurrence of MI with high efficacy. The results of the ceRNA network
suggest that hub genes may be cross-regulated by various lncRNAs and miRNAs. In addition,
10 drugs, including 2H-1-benzopyran, Nifuroxazide, and Bepridil, were predicted to be potential
therapeutic agents for MI.

Conclusion:

Our study identifies three promising genes associated with the progression of
chromatin regulators (CRs)-related myocardial infarction (MI) and immune cell infiltration, including
Dual-specificity phosphatase 1 (DUSP1), growth arrest and DNA damage-inducible 45
(GADD45A), and Jun dimerization protein 2 (JDP2), which might be worthy of further study.
Differential miRNA Profiling Reveals miR-4433a-5p as a Key Regulator of
Chronic Obstructive Pulmonary Disease Progression via PIK3R2-
mediated Phenotypic Modulation
Authors: Tao Siming , Liao Chunyan , Wang Yide , Xu Dan , Li Zheng , Li Fengsen
Published: November 2023

Objective:

In this study, a high-throughput sequencing technology was used to screen
the differentially expressed miRNA in the patients with "fast" and "slow" progression of chronic
obstructive pulmonary disease (COPD). Moreover, the possible mechanism affecting the progression
of COPD was preliminarily analyzed based on the target genes of candidate miRNAs.

Methods:

The "fast" progressive COPD group included 6 cases, "slow" and Normal progressive
COPD groups included 5 cases each, and COPD group included 3 cases. The peripheral blood
samples were taken from the participants, followed by total RNA extraction and high throughput
miRNA sequencing. The differentially expressed miRNAs among the progressive COPD groups
were identified using bioinformatics analysis. Then, the candidate miRNAs were externally verified.
In addition, the target gene of this miRNA was identified, and its effects on cell activity,
cell cycle, apoptosis, and other biological phenotypes of COPD were analyzed.

Results:

Compared to the Normal group, a total of 35, 16, and 7 differentially expressed miRNAs
were identified in the "fast" progressive COPD, "slow" progressive COPD group, and
COPD group, respectively. The results were further confirmed using dual-luciferase reporter assay
and transfection tests with phosphoinositide- 3-kinase, regulatory subunit 2 (PIK3R2) as a
target gene of miR-4433a-5p; the result showed a negative regulatory correlation between the
miRNA and its target gene. The phenotype detection showed that the activation of the phosphatidylinositol
3 kinase (PI3K)/protein kinase B (AKT) signaling pathway might participate in the
progression of COPD by promoting the proliferation of inflammatory A549 cells and inhibiting
cellular apoptosis.

Conclusions:

MiR-4433a-5p can be used as a marker and potential therapeutic target for the
progression of COPD. As a target gene of miR-4433a-5p, PIK3R2 can affect the progression of
COPD by regulating phenotypes, such as cellular proliferation and apoptosis.
Exploring Asthma Mechanism of Belamcanda Chinensis by “Dose–effect Weighted Coefficient” Network Pharmacology and Experiment Validation
Authors: Zhang Kaiyue , Lv Jingwei , Shen Jiaming , Zhang Nanxi , Gao Xiaochen , Wang Yuelong , Li Chunnan , Sun Jiaming
Published: November 2023

Background:

Asthma is a chronic inflammatory disease of the airways that seriously
endangers human health. Belamcanda chinensis (BC), a traditional Chinese medicine, has been
used to counteract asthma as it has been shown to possess anti-inflammatory and regulatory immunity
properties.

Objective::

The study aimed to investigate the mechanisms of action of BC in the treatment of
asthma; a “dose–effect weighted coefficient” network pharmacology method was established to
predict potential active compounds.

Methods:

Information on the components and content of BC was obtained by UPLC-QEOrbitrap-
MS spectrometry. Based on BC content, oral bioavailability, and molecular docking
binding energy, dose-effect weighting coefficients were constructed. With the degree greater than
average as the index, a protein–protein interaction (PPI) database was used to obtain the core key
targets for asthma under dose–effect weighting. GO function and KEGG pathway analyses of the
core targets were performed using DAVID software. Finally, MTT and ELISA assays were used
to assess the effects of active components on 16HBE cell proliferation.

Results:

The experimental results using the 16HBE model demonstrated BC to have a potential
protective effect on asthma. Network pharmacology showed SYK, AKT1, and ALOX5 to be the
main key targets, and Fc epsilon RI as the promising signaling pathway. Eight components, such
as tectoridin, mangiferin, luteolin, and isovitexin were the main active compounds, Finally, we
analyzed the LPS-induced 16HBE proliferation of each active ingredient. Based on the activity
verification study, all five predicted components promoted the proliferation of 16HBE cells. These
five compounds can be used as potential quality markers for asthma.

Conclusion:

This study provides a virtual and practical method for the simple and rapid screening
of active ingredients in natural products.
Transcutaneous Electrical Acupoint Stimulation Improves Postoperative Nutrition and Promotes Early Recovery of Gastrointestinal Function in Patients with Colorectal Cancer
Authors: Li Xia , Kou Zhijian , Liu Ruijuan , Zhou Zhendong , Mei Ju , Yan Wenjun
Published: November 2023

Objective:

To investigate the effect of transcutaneous electrical acupoint stimulation
(TEAS) on the postoperative nutritional status and recovery of gastrointestinal function in colorectal
cancer patients.

Methods:

Sixty-five patients with ASA grade I-II, undergoing laparoscopic radical colorectal
cancer surgery under elective general anesthesia were selected. They were divided into two
groups according to the random number table method: the TEAS group (T group) and the sham
stimulation group (S group). Two groups of patients were given separate transcutaneous electrical
acupoint stimulation and sham stimulation for 30 min at the Hegu (LI4), Neiguan (PC6),
Zusanli (ST36), Shangjuxu (ST37), Xiajuxu (ST39), and Sanyinjiao (SP6) points. The intervention
time point from the day before surgery, 30 minutes before the start of anesthesia induction,
at the start of skin incision, and at the end of surgery to the first, second, and third postoperative
days. Changes in serum total protein (TP), albumin (ALB), prealbumin (PA), and transferrin
(TRF) were observed, postoperative recovery of gastrointestinal function, and the incidence of
postoperative complications were observed.

Results:

There was no statistical difference between the general data of the two groups; TP, ALB,
PA, and TRF in both groups decreased significantly (P<0.05) on postoperative day 1 and 3 compared
with those on preoperative day 1. TP, ALB, PA, and TRF were significantly higher in patients
in group T than in group S on postoperative days 3 and 7, and the differences were statistically
significant (P<0.05). The time to first ventilation, time to defecation, and time to liquid diet were
all significantly shorter in group T than in group S. The difference was statistically significant
(P<0.05). The incidence of postoperative nausea, vomiting, and abdominal distension was significantly
lower in group T than in group S, with a significant statistical difference (P<0.05).

Conclusion:

Transcutaneous electrical acupoint stimulation can improve postoperative serum
protein levels and promote postoperative early recovery in patients with colorectal cancer.
Ziyin Bushen Fang improves Diabetic Osteoporosis by Inhibiting Autophagy
and Oxidative Stress In vitro and In vivo
Authors: Jiang Bo , Mou Yan Jie , Zhang Xian Mei , Lu Kun , Xie Ping , Rao Yan Ling , Cong Ze Wei , Sun Qin guo
Published: November 2023

Objective::

Diabetic osteoporosis (DOP) belongs to the group of diabetes-induced secondary
osteoporosis and is the main cause of bone fragility and fractures in many patients with
diabetes. The aim of this study was to determine whether Ziyin Bushen Fang (ZYBSF) can improve
DOP by inhibiting autophagy and oxidative stress.

background:

The aim of this experiment is to study whether Ziyin Bushen Fang (ZYBSF) can treat DOP through autophagy and oxidative stress.

Methods::

Type 1 diabetes mellitus (T1DM) was induced in rats using a high-fat high-sugar diet
combined with streptozotocin. Micro-CT scanning was used to quantitatively observe changes in
the bone microstructure in each group. Changes in the serum metabolites of DOP rats were analyzed
using UHPLC-QTOF-MS. The DOP mouse embryonic osteoblast precursor cell model
(MC3T3-E1) was induced using high glucose levels.

Results::

After ZYBSF treatment, bone microstructure significantly improved. The bone mineral
density, trabecular number, and trabecular thickness in the ZYBSF-M and ZYBSF-H groups significantly
increased. After ZYBSF treatment, the femur structure of the rats was relatively intact,
collagen fibers were significantly increased, and osteoporosis was significantly improved. A total
of 1239 metabolites were upregulated and 1527 were downregulated in the serum of T1DM and
ZYBSF-treated rats. A total of 20 metabolic pathways were identified. In cellular experiments,
ZYBSF reduced ROS levels and inhibited the protein expression of LC3II / I, Beclin-1, and p-
ERK.

Conclusion::

ZYBSF may improve DOP by inhibiting the ROS/ERK-induced autophagy signaling
pathway.
Acupuncture Increased the Number of Retrieved Oocytes in a Mouse Model of POR: The Involvement of DNA Methylation in the Oocytes
Authors: Wang Mengjing , Li Zimeng , Xiong Yueheng , Yuan Rongli , Zhu Xinyun , Chen Xin , Wang Tianyu , Li Zhi , Wu Jie
Published: November 2023

Background:

Poor ovarian response (POR) reduces the success rate of in vitro fertilization
mainly because of fewer oocytes retrieved. Acupuncture (Ac) therapy can improve the number
of retrieved oocytes in the controlled ovarian stimulation program. The role of Ac in the corresponding
epigenetic mechanism of POR has not been studied.

Objective:

This study was conducted to determine the effect of Ac on the number of retrieved
oocytes and its role in DNA methylation in a mouse model of POR.

Methods::

Forty C57BL/6N female mice with normal estrous cycles were randomly classified into
4 groups of 10 each: control (Con) group, Ac-Con group, POR group, and Ac-POR group. Mice
in POR and Ac-POR groups received a gastric gavage of Tripterygium wilfordii polyglycoside
suspension of 50 mg/kg-1 once a day for 14 consecutive days. Ac was applied at “Shenting” (DU
24), “Guanyuan” (CV 4), “Zusanli” (ST 36), and “Shenshu” (BL 23) in the Ac-POR group for 10
min per session, once a day for 14 consecutive days. All four groups were stimulated with pregnant
mare serum gonadotropin and human chorionic gonadotropin, and the number of retrieved oocytes
and proportion of mature oocytes were recorded. The DNA methylation level in a single mouse
oocyte in each group was analyzed using single-cell genome-wide bisulfite sequencing (scBSseq),
and key pathways were identified using GO and KEGG enrichment analyses.

Results:

A dissecting microscope revealed that the Ac therapy improved the number of retrieved
oocytes compared with the POR group (p < 0.05). ScBS-seq showed that there was no significant
change in global DNA methylation levels between the POR model and control group mice. However,
differences were primarily observed in the differentially methylated regions (DMRs) of each
chromosome, and Ac decreased global DNA methylation. DMR analysis identified 13 genes that
may be associated with Ac treatment. Cdk5rap2 and Igf1r, which mediate germ cell apoptosis,
growth, and development, maybe most closely related to the Ac treatment of POR. KEGG analysis
revealed that differentially expressed genes were mainly enriched in Wnt, GnRH, and calcium
signaling pathways. The genes were closely related to the regulation of POR via Ac.

Conclusion:

The results suggest that DNA methylation in oocytes is related to the development
of POR and that the role of Ac in affecting DNA methylation in oocytes is associated with the
Wnt, GnRH, and calcium signaling pathways as well as Cdk5rap2 and Igf1r in POR mice.
Establishment and Validation of the Novel Necroptosis-related Genes for Predicting Stemness and Immunity of Hepatocellular Carcinoma via Machine-learning Algorithm
Authors: Li Yao-Ting , Zeng Xue-Zhen
Published: November 2023

Background:

Necroptosis, a recently identified mechanism of programmed cell death,
exerts significant influence on various aspects of cancer biology, including tumor cell proliferation,
stemness, metastasis, and immunosuppression. However, the role of necroptosis-related
genes (NRGs) in Hepatocellular Carcinoma (HCC) remains elusive.

Methods:

In this study, we assessed the mutation signature, copy number variation, and expression
of 37 NRGs in HCC using the TCGA-LIHC dataset. We further validated our results using the
ICGC-LIRI-JP dataset. To construct our prognostic model, we utilized the least absolute shrinkage
and selection operator (LASSO), and evaluated the predictive efficacy of the NRGs-score using
various machine learning algorithms, including K-M curves, time-ROC curves, univariate and
multivariate Cox regression, and nomogram. In addition, we analyzed immune infiltration using
the CIBERSOFT and ssGSEA algorithms, calculated the stemness index through the one-class
logistic regression (OCLR) algorithm, and performed anti-cancer stem cells (CSCs) drug sensitivity
analysis using oncoPredict. Finally, we validated the expression of the prognostic NRGs
through qPCR both in vitro and in vivo.

Results:

About 18 out of 37 NRGs were found to be differentially expressed in HCC and correlated
with clinical outcomes. To construct a prognostic model, six signature genes (ALDH2, EZH2,
PGAM5, PLK1, SQSTM1, and TARDBP) were selected using LASSO analysis. These genes were
then employed to categorize HCC patients into two subgroups based on NRGs-score (low vs.
high). A high NRGs score was associated with a worse prognosis. Furthermore, univariate and
multivariate Cox regression analyses were performed to confirm the NRGs-score as an independent
risk factor. These analyses revealed strong associations between NRGs-score and critical factors,
such as AFP, disease stage, and tumor grade in the HCC cohort. NRGs-score effectively
predicted the 1-, 3-, and 5-year survival of HCC patients. Immune infiltration analysis further
revealed that the expression of immune checkpoint molecules was significantly enhanced in the
high NRGs-score group. Stemness analysis in the HCC cohort showed that NRGs-score was positively
correlated with mRNA stemness index, and patients with high NRGs-score were sensitive
to CSCs inhibitors. The findings from the external validation cohort provided confirmation that
the NRGs-score presented a trait with universal applicability in accurately predicting the survival
of HCC. Additionally, the six prognostic genes were consistently differentially expressed in both
the HCC cell line and the mouse HCC model.

Conclusions:

Our study demonstrated the pivotal role of NRGs in promoting stemness and immune
suppression in HCC and established a robust model which could successfully predict HCC prognosis.
The Prognostic Hub Gene POLE2 Promotes BLCA Cell Growth via the PI3K/AKT Signaling Pathway
Authors: Jiang Dongzhen , Zhang Huawei , Yin Bingde , He Minke , Lu Xuwei , He Chang
Published: November 2023

Background::

BLCA is a common urothelial malignancy characterized by a high recurrence rate. Despite its prevalence, the molecular mechanisms underlying its development remain unclear.

Aims::

This study aimed to explore new prognostic biomarkers and investigate the underlying mechanism of bladder cancer (BLCA).

Objective::

The objective of this study is to identify key prognostic biomarkers for BLCA and to elucidate their roles in the disease.

Methods::

We first collected the overlapping DEGs from GSE42089 and TCGA-BLCA samples for the subsequent weighted gene co-expression network analysis (WGCNA) to find a key module. Then, key module genes were analyzed by the MCODE algorithm, prognostic risk model, expression and immunohistochemical staining to identify the prognostic hub gene. Finally, the hub gene was subjected to clinical feature analysis, as well as cellular function assays.

Results::

In WGCNA on 1037 overlapping genes, the blue module was the key module. After a series of bioinformatics analyses, POLE2 was identified as a prognostic hub gene in BLCA from potential genes (TROAP, POLE2, ANLN, and E2F8). POLE2 level was increased in BLCA and related to different clinical features of BLCA patients. Cellular assays showed that si-POLE2 inhibited BLCA proliferation, and si-POLE2+ 740Y-P in BLCA cells up-regulated the PI3K and AKT protein levels.

Conclusion::

In conclusion, POLE2 was identified to be a promising prognostic biomarker as an oncogene in BLCA. It was also found that POLE2 exerts a promoting function by the PI3K/AKT signaling pathway in BLCA.
Mitochondrial Proteins as Metabolic Biomarkers and Sites for Therapeutic
Intervention in Primary and Metastatic Cancers
Authors: Robledo-Cadena Diana Xochiquetzal , Pacheco-Velazquez Silvia Cecilia , Vargas-Navarro Jorge Luis , Padilla-Flores Joaquín Alberto , Moreno-Sanchez Rafael , Rodríguez-Enríquez Sara
Published: November 2023

Accelerated aerobic glycolysis is one of the main metabolic alterations in cancer, associated
with malignancy and tumor growth. Although glycolysis is one of the most studied properties
of tumor cells, recent studies demonstrate that oxidative phosphorylation (OxPhos) is the main ATP
provider for the growth and development of cancer. In this last regard, the levels of mRNA and protein
of OxPhos enzymes and transporters (including glutaminolysis, acetate and ketone bodies catabolism,
free fatty acid β-oxidation, Krebs Cycle, respiratory chain, phosphorylating system- ATP
synthase, ATP/ADP translocator, Pi carrier) are altered in tumors and cancer cells in comparison to
healthy tissues and organs, and non-cancer cells. Both energy metabolism pathways are tightly regulated
by transcriptional factors, oncogenes, and tumor-suppressor genes, all of which dictate their
protein levels depending on the micro-environmental conditions and the type of cancer cell, favoring
cancer cell adaptation and growth. In the present review paper, variation in the mRNA and protein
levels as well as in the enzyme/ transporter activities of the OxPhos machinery is analyzed. An
integral omics approach to mitochondrial energy metabolism pathways may allow for identifying
their use as suitable, reliable biomarkers for early detection of cancer development and metastasis,
and for envisioned novel, alternative therapies.
Cinchonine: A Versatile Pharmacological Agent Derived from Natural
Cinchona Alkaloids
Authors: Parveen Shahnaz , Maurya Nidhi , Meena Abha , Luqman Suaib
Published: November 2023

Background:

Cinchonine is one of the Cinchona alkaloids that is commercially extracted
from the Peruvian bark of Cinchona officinalis L. (Family: Rubiaceae). It is also obtained in
much lower quantities from other species of Cinchona, such as Cinchona calisaya, Cinchona succirubra,
and Cinchona pubescens, and in some other plants, such as Remijia peruviana. Cinchonine
has been historically used as an anti-malarial agent. It also has a wide range of other biological
properties, including anti-cancer, anti-obesity, anti-inflammatory, anti-parasitic, antimicrobial,
anti-platelet aggregation, and anti-osteoclast differentiation.

Aim and Objective:

This review discusses the pharmacological activity of cinchonine under different
experimental conditions, including in silico, in vitro, and in vivo. It also covers the compound's
physicochemical properties, toxicological aspects, and pharmacokinetics.

Methodology:

A comprehensive literature search was conducted on multiple online databases,
such as PubMed, Scopus, and Google Scholar. The aim was to retrieve a wide range of review/research
papers and bibliographic sources. The process involved applying exclusion and inclusion
criteria to ensure the selection of relevant and high-quality papers.

Results:

Cinchonine has numerous pharmacological properties, making it a promising compound
for various therapeutic applications. It induces anticancer activity by activating caspase-3 and
PARP-1, and triggers the endoplasmic reticulum stress response. It up-regulates GRP78 and promotes
the phosphorylation of PERK and ETIF-2α. Cinchonine also inhibits osteoclastogenesis, inhibiting
TAK1 activation and suppressing NFATc1 expression by regulating AP-1 and NF-κB. Its
potential anti-inflammatory effects reduce the impact of high-fat diets, making it suitable for targeting
obesity-related diseases. However, research on cinchonine is limited, and further studies
are needed to fully understand its therapeutic potential. Further investigation is needed to ensure
its safety and efficacy in clinical applications.

Conclusion:

Overall, this review article explains the pharmacological activity of cinchonine, its
synthesis, and physicochemical properties, toxicological aspects, and pharmacokinetics.
Secondary Degeneration of White Matter Tract following Basal Ganglia
Infarction: A Longitudinal Diffusion Tensor Imaging Study
Authors: Zheng Shasha , Lin Qixiang , Zhang Miao , Liu Hesheng , He Yong , Lu Jie
Published: November 2023

Introduction::

We explored the relationship between secondary degeneration of white matter (WM) tracts and motor outcomes after left basal ganglia infarction
and investigated alterations in the diffusion indices of WM tracts in distal areas.

Methods::

Clinical neurological evaluations were accomplished using the Fugl–Meyer scale (FMS). Then, the fractional anisotropy (FA) of the bilateral
superior corona radiata (SCR), cerebral peduncle (CP), corticospinal tracts (CST), and corpus callosum (CC) were measured in all patients and
control subjects.

Results::

Regional-based analysis revealed decreased FA values in the ipsilesional SCR, CP, and CST of the patients, compared to the control subjects at 5-
time points. The relative FA (rFA) values of the SCR, CP, and CST decreased progressively with time, the lowest values recorded at 90 days
before increasing slightly at 180 days after stroke. Compared to the contralateral areas, the FA values of the ipsilesional SCR and CST areas were
significantly decreased (P=0.023), while those of the CP decreased at 180 days (P=0.008). Compared with the values at 7 days, the rFA values of
the ipsilesional SCR and CP areas were significantly reduced at 14, 30, and 90 days, while those in the CST area were significantly reduced at 14,
90, and 180 days. The CP rFA value at 7 days correlated positively with the FM scores at 180 days (r=0.469, P=0.037).

Conclusion::

This study provides an objective, comprehensive, and automated protocol for detecting secondary degeneration of WM, which is important in
understanding rehabilitation mechanisms after stroke.
Radiologists’ and Radiographers’ Perspectives on Artificial Intelligence in
Medical Imaging in Saudi Arabia
Authors: Alyami Ali S. , Majrashi Naif A. , Shubayr Nasser A.
Published: November 2023

Introduction::

Artificial intelligence (AI) in medical imaging rapidly expands regarding image processing and interpretation. Therefore, the aim was to explore
radiographers’ and radiologists’ perceptions and attitudes towards AI use in medical imaging technologies in Saudi Arabia.

Methods::

The survey was distributed online, and responses were collected from 173 participants nationwide. Data analysis was performed using SPSS
Statistics (version 27).

Results::

The participants scored an average of 1.7, 1.6, and 1.8 on a scale of 1–3 for attitudinal perspectives on clinical application and the positive and
negative impact of integrating AI technology in diagnostic radiology. Lack of knowledge (43.9%) and perceived cyber threats (37.7%) were the
most cited factors hindering AI implementation in Saudi Arabia.

Conclusion::

The radiographradiology radiologists in this study had a favorable attitude toward AI integration in diagnostic radiology; nonetheless, concerns
were raised about data protection, cyber security, AI-related errors, and decision-making challenges.
External Validation of Ultrasound Radiomics for Small (≤ 4 cm) Renal Mass
Differentiation: A Comparison with Radiologists
Authors: Liang Ming , Dong Licong , Ou Bing , Zhao Xinbao , Wu Jiayi , Qiu Haolin , Ye Mengting , Luo Baoming
Published: November 2023

Background::

Renal cell carcinoma, especially in small renal masses (≤ 4 cm) (SRM), has increased. Pathological analysis revealed a high proportion of benign
masses, highlighting the urgent need for precise SRM differentiation.

Objectives::

This research aimed to independently validate the performance of machine learning-based ultrasound (US) radiomics analysis in differentiating
benign from malignant SRM, and to compare its performance with that of radiologists.

Methods::

A total of 499 patients from two hospitals were retrospectively included in this study and divided into two cohorts. US images were used to extract
radiomics features. To obtain the most robust features, inter-observer correlation coefficient, Spearman correlation coefficient, and least absolute
shrinkage and selection operator methods were applied for feature selection. Three models were developed in the training data using the stochastic
gradient boosting algorithm, including a clinical model, a radiomics model, and a combined model that integrated clinical factors and radiomics
features. The performance of these models was evaluated in the independent external validation data, including discrimination, calibration, and
clinical usefulness, and compared with pooled radiologists' assessments.

Results::

The AUCs of the clinical, radiomics, and combined models were 0.844, 0.942, and 0.954, respectively. The radiomics and combined models
significantly outperformed the clinical model (all p < 0.05), while no significant difference was observed between them (p = 0.32). The radiomics
and combined models showed good discrimination and calibration. Decision curve analysis exhibited that the combined model had clinical
usefulness. Compared with the pooled radiologists’ assessment (AUC, 0.799), the combined model showed superior classification results (p <
0.01) and higher specificity (p < 0.01) with similar sensitivity (p = 0.62).

Conclusion::

The combined model incorporating clinical factors and radiomics features accurately distinguished benign from malignant SRM.
Carbon Nanotubes: A Targeted Drug Delivery against Cancer Cell
Authors: Kumar Prashant , Pandey Surya Nath , Ahmad Farman , Verma Anurag , Sharma Himanshu , Ashique Sumel , Bhattacharyya Subhra Prakash , Bhattacharyya Indrani , Kumar Shubneesh , Mishra Neeraj , Garg Ashish
Published: November 2023

Drug delivery in human subjects has been the most difficult task since the ancient
time of the medical sector. An ideal drug delivery system is, one that minimizes the adverse
effects and maximizes the desired effects of the drug candidate. Various drug delivery systems
have been developed that may have some kind of advantages and disadvantages, among them
targeted drug delivery system is more preferable and convenient which may employ various
nanoparticles or other materials for the drug delivery at the specified site of action. In this, the
authors elaborately and comprehensively explained the role of recent carbon nanotubes (CNTs)
in targeted drug delivery systems (specifically for targeting cancerous cells). The authors also
described the methods of preparation of CNTs, characterization techniques for CNTs, cellular
penetration of, CNTs, and the associated toxicities with CNTs. Carbon nanotubes are preferable
to other nanoparticles because they are more electrically, mechanically, and organically stable
than others, they can carry more amount of drug in comparison to other nanoparticles and their
functionalization property makes them more attractive as a carrier molecule for targeting any
root cause of the disease.
Self-Assembled Nanoparticle-Forming Derivatives of Dextrin-Conjugated Polyethylenimine Containing Urethane Bonds for Enhanced Delivery of Interleukin-12 Plasmid
Authors: Keshavarz Valiollah , Kazemi Maryam , Khalvati Bahman , Dehshahri Ali , Sadeghpour Hossein
Published: November 2023

Background and Objective:

In the present investigation, low molecular weight polyethylenimine
(LMW PEI, 1.8 kDa PEI) was conjugated to dextrin via urethane units and tested
to transfer plasmid encoding interleukin-12 (IL-12) plasmid. Although high molecular weight
PEI (HMW PEI, 25 kDa PEI) has shown substantial transfection efficiency, its wide application
has been hampered due to considerable cytotoxicity. Therefore, LMW PEI with low toxic effects
was used as the core of our gene transfer construct.

Methods:

LMW PEI was conjugated to dextrin via urethane units to improve its biophysical
characteristics as well as cytotoxic effects. The conjugates were characterized in terms of buffering
capacity, plasmid DNA condensation ability, particle size, and zeta potential as well as protection
against enzymatic degradation. In Vitro experiments were carried out to evaluate the
ability of these LMW PEI conjugates to transfer plasmid encoding human interleukin-12 (hIL-
12) to the cells. The MTT assay was performed to measure the cell-induced toxicity of the conjugates.

Results:

The results of our study demonstrated that the PEI derivatives with higher amounts of
amine content (i.e. higher conjugation degrees) have considerable buffering capacity and plasmid
condensation ability. These conjugates could condense plasmid DNA at Carrier to Plasmid
ratios (C/P) ≥2 and form polyplexes at the size range of 120-165 nm while their zeta potential
was around 5.5-8.5 mV. The results of transfection efficiency demonstrated that the level of IL-
12 production increased by 2-3 folds compared with unmodified LMW PEI while the level of
cytotoxicity was not higher than 20%.

Conclusion:

The strategy used in this study shows a promising way to prepare gene carriers
with high transfection efficiency and low toxicity.
In Situ Photo Responsive Biodegradable Nanoparticle Forming Intrauterine Implant for Drug Delivery to Treat Ovarian Diseases: A Rationale-based Review
Authors: Corrie Leander , Kommineni Nagavendra , Kaur Jaskiran , Awasthi Ankit , Gundaram Raghunandan , Kukati Latha
Published: November 2023

:

Ovarian disease constitutes various types of endocrine disorders, such as polycystic
ovarian syndrome (PCOS), ovarian cancer, premature ovarian failure, ovarian endometriosis,
and ovarian cysts. The prevalence of ovarian-related diseases is highly vulnerable in the world.
The utility of various drug delivery systems for ovarian diseases has resulted in varied success.
Moreover, most of them lead to severe adverse effects and are incapable of ameliorating the
signs and symptoms of the condition. Intrauterine devices (IUDs) have positioned themselves as
a mechanism to deliver the drug for various ovarian-related diseases. Thereby avoiding various
stability-related issues arising due to various physiological barriers of the female reproductive
tract. However, the use of intrauterine devices for drug delivery to the ovaries has not been fully
explored. This is attributed to the fact that they cause cysts in the ovaries and skepticism among
patients and physicians. Photo-sensitive devices are an appealing approach for managing disorders
affecting the ovaries. Photo-sensitive in situ forming intrauterine implants (IUIs) have several
advantages, including simplicity in application, reduced invasiveness, as well as improved
site-specific drug release control. Polymeric nanoparticles (PNPs) loaded with a drug may be a
suitable choice to provide sustained release, alter the pharmacokinetics, and reduce the dose and
dosing frequency. The current manuscript hypothesizes the utility of a PNP-loaded biodegradable
photo-responsive intrauterine implantable device as an alternate novel strategy for ameliorating
ovarian-related diseases.
General Physical Examination
Authors: Ghaly Yousif Nasser , Hadi Najah R. , Alamran Fadhil G.
Published: November 2023

Physical examination is a fundamental aspect of medical practice that
involves a systematic evaluation of a patient's body to assess their overall health status
and identify any signs of illness or abnormalities. It is typically performed by
healthcare professionals, such as physicians, nurses, or other trained medical personnel.
The physical examination can provide valuable information that aids in the diagnosis,
treatment, and monitoring of various medical conditions. The physical examination,
thoughtfully performed, should yield 20% of the data necessary for patient diagnosis
and management. The present chapter is mainly focused on how to apply physical
general examination
'I'm Real, Not You': Roles and Discourses of Trans Exclusionary Women's and Feminist Movements in Anti-gender and Right-wing Populist Politics
Authors: House Claire C. A.
Published: November 2023

This article offers a comparative inquiry concerning the rise in visibility, relevance, and power of trans exclusionary women’s and feminist movements in Canada and the United Kingdom (UK) between 2015 and 2022.  It focuses on two case studies concerning trans rights: the successful campaign for Bill C-16 in Canada, and failed reform of the Gender Recognition Act 2004 in the UK. In both cases, key streams within trans exclusionary women’s and feminist movements increasingly engage in collaborative action with right-wing populist-centered anti-gender coalitions, which include right-wing religious, conservative, and right-wing extremist actors, from approximately 2016. It argues that a key role of women’s and feminist actors in these coalitions is to help legitimize, amplify, and give meaning to anti-gender and right-wing populist appeals and, therein, the politics of exclusion they promote. This occurs in part, it is argued, through symbolic appeals concerning authenticity and the non-materiality of trans lives; the promotion of narratives concerning conflicts in rights; and the provision of strong imagery, narrative, and emotional appeals concerning threat. These broad developments have had various important effects. In the UK, the combination of so-called ‘radical’ as well as ‘traditional’ actors within anti-gender coalitions, has been critical in challenging progress towards trans and broader (Lesbian, Gay, Bi, Trans, Intersex, and Queer) LGBTIQ+ rights. In Canada, although anti-gender movements have enjoyed less policy success during this period, women’s and feminist actors have helped popularize and provide legitimacy to wider coalitions. 