bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel pH-sensitive Nanocomposite Based on Graphene Oxide for
Improving Doxorubicin Release
Authors: Kachousangi Marziye Javaheri , Shadboorestan Amir , Shamsian Azam , Amini Mohsen , Atyabi Fatemeh , Ghahremani Mohammad Hossein 
Published: April 2023

Background:
Doxorubicin (DOX) as a chemotherapeutic drug has been widely used for
treatment of cancer but because of adverse side effects of this drug, different drug delivery systems have
been tested. One of them has been immobilization of DOX on the graphene oxide (GO) sheets through
non-covalent interactions (GO-DOX) with high efficiency however the release was very low and slow
due to strong forces between DOX and GO.

Objective:
The aim of this research was to increase the release of DOX and this goal was achieved
through the covalent binding of DOX to the GO-poly(ethyleneimine) 2KDa conjugate.

Methods:
Because of the reliable results, ease of operation, safety and high reproducibility, MTT was chosen to evaluate the cytotoxicity of samples. The MTT assay confirmed the advantage of this nanocarrier in comparison to the physical loading of DOX on GO sheets. Loading of DOX via hydrazide bond was as low as 4% versus near 75% physical loading of drug. While hydrazide bond-containing nanocomposite was 4 to 6 fold more toxic than GO-DOX.A novel nanocarrier for delivering DOX was fabricated using GO as a basic plane for conjugating
and assembling other compounds. DOX was attached to GO-poly(ethyleneimine) 2KDa conjugate
via a linker containing hydrazide bond. Drug loading and release was investigated at pH 7.5 and pH
5.5. Cytotoxicity was determined by MTT on MCF7 cells and compared with previous nanocarrier.

Results:
The fabrication of the nanocarrier and the covalent attachment of DOX to the nanocarrier were
confirmed through FT-IR spectroscopy. The capacity of nanocarrier to load drug was as high as 383%.
96% of initial drug was loaded in the nanocarrier. The weight percentage of the drug in the nanocarrierdrug
conjugate was 79%. Release of drug at pH 5.5 was two times more than release at pH 7.5 and this
evidence supports conjugation of DOX to nanocarrier through hydrazide bond and pH-sensitivity of
related bond. Because of the reliable results, ease of operation, safety and high reproducibility, MTT
was chosen to evaluate the cytotoxicity of samples. Nanocarrier didn’t show significant toxicity even at
high concentrations. IC50 value for chemically-bound DOX to hydrazide-containing GO nanocomposite
was 9.5 μg/ml whereas the IC50 value for GO-DOX was 39 μg/ml after 72 h. Loading of DOX via hydrazide
bond was as low as 4% versus near 75% physical loading of drug while hydrazide bondcontaining
nanocomposite was 4 to 6 fold more toxic than GO-DOX.

Conclusion:
Based on the obtained data, the covalent attachment of DOX to the nanocarrier through
hydrazide linkers was an interesting idea that increased drug release and toxicity despite much lower
percentage of covalent attachment compared to non-covalent immobilization.
As could be concluded from this study, nanocarriers based on hydrazide bond could be a good candidate for
drug delivery.
SARS-CoV-2 Omicron Variant in Medicinal Chemistry Research
Authors: Souza Rocha Weslany , Zhan Peng , Ferreira da Silva-Júnior Edeildo 
Published: April 2023

Abstract:
The Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respirato-ry syndrome Coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths and threatens public health and safety. Nowadays, modern society has faced a new challenging problem, the emergence of novel SARS-CoV-2 variants of concern (VOCs). In this context, the Omicron (B.1.1.529) vari-ant, having more than 60 mutations when compared to its ancestral wild-type virus, has infected many individuals around the world. It is rapidly spread person-to-person due to its increased trans-missibility. Additionally, it was demonstrated that this newest variant and its subvariants have the capability of evading the host immune system, being resistant to neutralizing antibodies. Moreover, it has been proven to be resistant to monoclonal antibodies and several different vaccines. This abil-ity is associated with a huge number of mutations associated with its spike (S) glycoprotein, which presents at least 15 mutations. These mutations are able to modify the way how this virus interacts with the host angiotensin-converting enzyme 2 (ACE2), increasing its infectivity and making the therapeutic alternatives more ineffective. Concerning its chymotrypsin-like picornavirus 3C-like protease (3CLpro) and RNA-dependent RNA polymerase (RdRp), it has been seen that some com-pounds can be active against different SARS-CoV-2 variants, in a similar mode than its wild-type precursor. This broad spectrum of action for some drugs could be attributed to the fact that the cur-rently identified mutations found in 3CLpro and RNA proteins being localized near the catalytic binding site, conserving their activities. Herein this review, we provide a great and unprecedented compilation of all identified and/or repurposed compounds/drugs against this threatening variant, Omicron. The main targets for those compounds are the protein-protein interface (PPI) of S protein with ACE2, 3CLpro, RdRp, and Nucleocapsid (N) protein. Some of these studies have presented on-ly in silico data, having a lack of experimental results to prove their findings. However, these should be considered here since other research teams can use their observations to design and investigate new potential agents. Finally, we believe that our review will contribute to several studies that are in progress worldwide, compiling several interesting aspects about VOCs associated with SARS-CoV-2, as well as describing the results for different chemical classes of compounds that could be prom-ising as prototypes for designing new and more effective antiviral agents.
Electrochemical Protein-based Bioanalytical Devices for Drug Analysis
Authors: Sanz Caroline G. , Diculescu Victor C. 
Published: April 2023

Abstract:
Proteins are vital components of living cells and the loss of their native functions has been associated with a wide variety of medical conditions. From this point of view, investigation of the protein microenvironment is crucial to support the development of therapeutic approaches capa-ble of ensuring cellular functions. Therefore, analytical assays for the detection, quantification, and characterization of proteins, drugs, and protein-drug complexes play an essential role in fundamen-tal research and clinical applications. Electrochemistry arises as an alternative methodology for fast assessment of proteins and drugs and is attractive due to the adaptability to miniaturization and scalability of electroanalytical devices, which then can be further employed as strategies towards personalized medical care. Thus, this review summarizes electrochemical investigations in the past 10 years on protein-based analytical devices and biosensors. A general overview of electrochemical assays that integrate proteins with nanostructured materials and conductive polymers is presented. Applications of electrochemical assays and biosensors were divided into four categories. First, those designed for drug screening strategies that focus on targeting specific intracellular, extracellular, or membrane protein subdomains to modulate their functions, aggregation/misfolding of proteins, and protein degradation pathways. Then, drug metabolism assays that involve mimicking natural meta-bolic pathways to identify potential safety and efficacy issues related to a drug or its metabolites. The third was dedicated to electrochemical drug delivery systems with anchored drugs in the form of bioconjugates, while the fourth was dedicated to electroanalytical methodologies for quantitative drug assays, where the electroactivity of the target species is often used to correlate the electro-chemical signal to their concentration.
Formulation and Characterization Studies of Paclitaxel Incorporated
Kollidon® SR and Chitosan Nanoparticles: An In vitro Evaluation for
Potential Use for Colorectal Cancer Treatment
Authors: Koca Özge Atasoy , Büyükköroğlu Gülay , Başaran Ebru 
Published: April 2023

Background:
Chemotherapy is regarded as first-line therapy in various cancer types besides surgical procedures. However, lack of cell selectivity and poor drug targeting to the cancer zone of the active agents results in accumulation in normal tissues with considerably high severe side effects. Therefore, novel drug delivery systems are required to enhance cancer treatment.

Objective:
In this study, Paclitaxel (PTX) incorporated Kollidon® SR (KSR) and Chitosan (CS) based polymeric nanoparticles were prepared for potential use for colorectal cancer treatment.

Methods:
Polymeric nanoparticles were prepared by spray dying method. Physicochemical characterization studies were performed with particle size (PS), polydispersity index (PDI), zeta potential (ZP), drug loading (DL %), encapsulation efficiency (EE %) and structural evaluations using differential scanning calorimetry (DSC), X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (1H-NMR) analyses. Cytotoxicity of the nanoparticles was screened on HT-29 (human colorectal adenocarcinoma) and HTC-15 (Dukes' type C, colorectal adenocarcinoma) cell lines with MTT assay.

Results:
Analysis revealed the successful incorporation of PTX into the polymeric lattices. Particles showed cytotoxic activity on HT-29 and HTC-15 cell lines, depending on the application dose after 48 hours. Nanoparticles also remained stable at 5°C ± 3°C and 25°C ± 2°C (60% ± 5 Relative Humidity (RH)) during the storage period of 6 months.

Conclusion:
As a result of the study, KSR and CS-based nanoparticles could be regarded as promising nano-carriers for improved therapeutic efficacy of PTX for colorectal cancer treatment.
Quinoline-based Anti-oncogenic Molecules: Synthesis and Biological
Evaluation
Authors: Sharma Shivangi , Singh Shivendra , Yadav Dhananjay 
Published: April 2023

Abstract:
Quinoline and its analogues are found in various natural products, many of which are active
pharmacophores with significant bioactivities. This article discussed the plethora of quinoline
derivatives and their analogues that have anti-cancer properties. The review will be helpful for the
scientific community since several possible anticancer drugs based on quinolines are discussed here.
In addition to this, the synthetic aspect of many such quinoline derivatives showing anti-cancer activities
is also revealed in this article. These quinoline-based anti-oncogenic molecules can be synthesized
using several acids, bases, and azides or with the help of reagents like Jone’s reagent and
Lawesson’s reagent.
Mesenchymal Stem Cell Therapy for Treating the Underlying Causes of
Diabetes Mellitus and Its Consequences
Authors: Esquivel Diana , Mishra Rangnath , Srivastava Anand 
Published: April 2023

Abstract:
Diabetes mellitus (DM) is a multifaceted pathological condition, which at present is being
considered an epidemic disease keeping the rampant rate of its increase in almost all population groups of
the world in consideration. Out of the two types of DM described, T1D is characterized as an autoimmune
condition that leads to the destruction of pancreatic β-cells by macrophages and T-cells, thereby, adversely
affecting the production of insulin. On the other hand, T2D, often caused by insulin resistance, is
commonly related to unhealthy habits, and therefore, it can be prevented in most cases. In both of the
conditions, high levels of proinflammatory cytokines like IL-6, TNF-α, and INF-ƴ, lead to chronic inflammation,
and elevated oxidative stress resulting in apoptosis and destruction of tissues. Although several
treatments are available to treat the symptoms, the underlying causes are not well addressed. One of
the most promising approaches to tackle the ill effects and the primary causes of DM is mesenchymal
stem cell (MSC) therapy. The use of MSC therapy, because of the immunomodulatory and regenerative
properties recorded in this type of cells in a number of experiments carried out in animal models and clinical
trials of the disease, has reported positive outcomes. This review covers the principal mechanisms of
action induced during MSC therapy in reference to the described pathophysiological pathways of both
T1D and T2D. In addition, how this therapeutic intervention can counteract the ill effects of this condition
leading to the promotion of tissue regeneration has been covered.
miRNA, siRNA, and lncRNA: Recent Development of Bioinformatics
Tools and Databases in Support of Combating Different Diseases
Authors: Chakraborty Chiranjib , Bhattacharya Manojit , Ranjan Sharma Ashish 
Published: April 2023

Abstract:
Today, the bioinformatics tool and database development are one of the most significant research
areas in computational biology. Computational biologists are developing diverse bioinformatics
tools and databases in the various fields of biological science. Nowadays, several non-coding RNAs
(ncRNA) have been studied extensively, which act as a mediator of the regulation of gene expression.
ncRNA is a functional RNA molecule that is transcribed from the mammalian genome. It also controls
the disease regulation pathway. Based on the size, ncRNA can be classified into three categories such as
small ncRNA (~18–30 nt), medium ncRNA (~30–200 nt), and long ncRNA (from 200 nt to several
hundred kb). The miRNA and siRNAs are two types of ncRNA. Various bioinformatics tools and databases
have recently been developed to understand the different ncRNAs (miRNAs, siRNAs, and
lncRNAs) disease association. We have illustrated different bioinformatics resources, such as in silico
tools and databases, currently available for researching miRNAs, siRNAs, and lncRNAs. Some bioinformatics-
based miRNA tools are miRbase, miRecords, miRCancer, miRSystem, miRGator, miRNEST,
mirtronPred and miRIAD, etc. Bioinformatics-based siRNA tools are siPRED, siDRM, sIR, siDirect
2.0. Bioinformatics-based lncRNAs tools are lncRNAdb v2, lncRNAtor, LncDisease, iLoc-lncRNA,
etc. These tools and databases benefit molecular biologists, biomedical researchers, and computational
biologists.
In silico Exploration of Phytochemical based Thiazolidinone- Caffeic Acid- Indole New Chemical Entities for Simultaneous Management of Diabetes and Hypertension- A Fascinating Study
Authors: Asgaonkar Kalyani , Patil Shital , Daga Yash , Gupta Manjish , Sagar Ashwini , Shevate Krishna , Mahadik Indrani , Randive Vrushali 
Published: April 2023

Background:Past few decades have witnessed the co-existence of diabetes and hypertension leading to other health disorders. Hence, it is imperative to look into new therapies for the treatment of both hypertension and diabetes simultaneously in order to gradually reduce the pill burden and subsequent side effects.Objective:The goal of the current work was to use several in silico methods to develop new entities that have both anti-diabetic and anti-hypertensive activity.Methods::Structure activity relationship was drawn from the literature considering Thiazolidinones (Anti diabetes), Indole (Antihypertensive) and naturally occurring polyphenols (Dual activity) for simultaneous management of hypertension and diabetes. Fifty-six new chemical entities were designed and subjected to ADME and docking studies. Based on the Lipinski filter, bioavailability and lead likeness nineteen molecules were further docked into three PDB’s (5Y2T, 4BVN, 1O8A).Results:The majority of the NCE’s have shown higher binding affinities than the standard drugs, with Compound 42 having the best results. Among nineteen NCE’s, 50% of the compounds have shown the involvement of Thiazolidinone, Indole and Catechol pharmacophores with prominent hydrogen bonds, hydrophobic, electrostatic and pi-pi stacking interactions with all three PDB’s signifying their potential dual activity. Most favourable interactions were shown by compound 42.Conclusion:The results obtained are encouraging for further exploration of the hit molecules for simultaneous treatment of the two diseases.
Vaginal dysbiosis as a factor contributing to the development of recurrent lower urinary tract infections
Authors: Kosova I. V. , Barsegian V. A. , Sinyakova L. A. , Lukianov I. V. , Kolbasov D. N. 
Published: April 2023

Introduction. It is known that women are significantly more likely to suffer from lower urinary tract infections (LUTIs) than men. Nowadays, there is growing evidence to demonstrate the impact of vaginal microbiota on the development of recurrent LUTIs.Objectives. To demonstrate the impact of vaginal microbiota disorders on the development of recurrent lower urinary tract infections.Materials & methods. Seventy-five women with recurrent LUTIs 19 – 76 years old were enrolled in this study. The examination was performed according to the algorithm developed in the Department of Urology and Surgical Andrology, Russian Medical Academy of Continuous Professional Education. Real-time PCR of vaginal epithelial cell scrapings (Femoflor 16) was performed to comprehensively evaluate the vaginal microbiota.Results. Vaginal dysbiosis was detected in 47/75 (62.7%) women with recurrent UTIs: moderate vaginal dysbiosis was detected in 25/75 (33.3%) women and severe dysbiosis — in 22/75 (29.3%) women. A moderate correlation between the presence/absence of vaginal dysbiosis and the number of LUTI recurrences over 6 months was found (r = 0.310; p = 0.007). Vaginal dysbiosis was significantly more common among peri- and postmenopausal women with recurrent LUTIs than reproductive women (OR = 4.85; 95% CI = 1.45 – 16.17).Conclusion. Vaginal dysbiosis contributes to the development of recurrent LUTIs with more relapses. Vaginal microbiota disorders and, consequently, recurrent LUTIs are more common in peri- and postmenopausal women than reproductive women.
Clinical portrait of an "ordinary" patient with benign prostatic hyperplasia and the efficacy of treating lower urinary tract symptoms
Authors: Medvedev V. L. , Efremov M. E. , Shornikov P. V. , Isayeva D. S. 
Published: April 2023

Introduction. Benign prostatic hyperplasia (BPH) is a common condition in aging men that is often associated with lower urinary tract symptoms (LUTS).Objective. To determine the clinical portrait of an "ordinary" patient with benign prostatic hyperplasia and develop an algorithm for improving the efficacy of treating lower urinary tract symptoms in benign prostatic hyperplasia.Materials & methods. The study included 112 BPH-patients who received tamsulosin therapy or a combination of tamsulosin + solifenacin for three months. After three months of therapy, the patients were divided into two groups depending on the effectiveness of therapy: group 1 — a positive result (n = 77); group 2 — no positive effect (n = 35). Due to the lack of efficacy in patients of group 2, a multichannel urodynamics was performed, according to the results of which the patients were prescribed treatment with a subsequent assessment of the result after 3 months.Results. After 3 months of therapy in patients of group 1, a decrease in pollakiuria was noted. Regression of obstructive and irritative symptoms was also observed, and the urination-associated quality of life (QoL) improved. The maximum urine flow rate (Q max) remained unchanged mainly. By the sixth month, the frequency of urination continued to decrease (11.05 vs 9.32 episodes; p = 0.022), as well as the improvement of other parameters (IPSS, QoL, Q max and post-void residual urine volume (PVR) (80.87 vs 56.17 ml; p = 0.012). The indicators of patients of group 2 following three months of therapy remained without significant changes. Sixteen patients underwent transurethral prostate resection, 19 patients underwent therapy correction, which allowed reducing the number of episodes of daily pollakiuria. The total IPSS score decreased by 4.37 compared to baseline (IPSS (obstructive) — 13.79 vs 7.26 pts; p = 0.032). The QoL value was 2.84 pts, Q max — 14.90 mL/s, PVR — 10.58 mL.Conclusion. 19.8% of BPH-patients are resistant to drug therapy. The ineffectiveness of therapy may be due to the severe BOO. In the absence of the effect of the therapy within 3 months, it is recommended to perform multichannel urodynamics. Correction of therapy according to the multichannel urodynamics data improves its effectiveness by the sixth month of treatment. Indicators of IPSS, Q max and PVR after 3 months of therapy allow predicting the effectiveness of therapy, or suspect the need for surgical treatment.
Corrección a TruDisp 2.0: una aplicación para el cálculo del desplazamiento verdadero (neto) de fallas [Rev. Mex. Cienc. Geol., 39 (2022), 285-292]
Authors: Nieto-Fuentes Ricardo , Nieto-Samaniego Angel Francisco , Xu Shunshan , Alaniz-Álvarez Susana Alicia 
Published: April 2023

La Tabla 2 publicada originalmente contiene algunos errores en los datos, aquí se presenta la Tabla con los datos correctos. Los autores lamentan el error.
Artículo original / original paperDOI: https://doi.org/10.22201/cgeo.20072902e.2022.3.1705
Participación y eficiencia técnica en la pequeña agricultura de la Provincia de Ñuble (Región del Bío-Bío, Chile)
Authors: Jaime Mónica M. , Salazar César A. , Novoa Loreto F. 
Published: April 2023

El propósito de este estudio es analizar los determinantes de la efi ciencia técnica de los pequeños agricultores de trigo de la Provincia de Ñuble (Chile), e indagar si existe una relación entre participación en organizaciones y eficiencia técnica. Utilizando información recopilada por medio de una encuesta, se estimó un modelo de fronteras estocásticas que incorpora factores específicos para cada productor. Los resultados sugieren que la propiedad del predio y tamaño del productor explican significativamente los niveles de eficiencia técnica. Se destaca además la importancia del capital social, medido a través de la participación en organizaciones, como una alternativa para alcanzar mayores niveles de eficiencia técnica. En este sentido, la participación en organizaciones podría constituirse en un importante factor de desarrollo para las comunidades rurales, al permitir compartir riesgos inherentes del negocio, diversificando su base productiva y ampliando las oportunidades para incrementar sus volúmenes de venta y alcanzar prácticas productivas innovadoras y eficientes. AbstractThe aim of this study is to analyze the determinants of technical efficiency of wheat small farmers in Ñuble Province (Chile), and to assess the relation between participation in organizations and technical efficiency. Using information collected by surveys, a stochastic frontier production function was estimated. The results show that property of the exploitation and size of farmers explain significantly the individual technical efficiency levels. The importance of social capital measured by participation in organization is enhanced as an alternative to achieve higher levels of technical efficiency. In this way, the participation in organization could transform into an important factor of development in rural communities through its contribution to share risks and diversify the production as well as by extending the opportunities to increase sales and reach more innovative and efficient practices.