bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alkaloids as Promising Agents for the Management of Insulin Resistance:
A Review
Authors: Amssayef Ayoub , Eddouks Mohamed 
Published: December 2023

Background:
Insulin resistance is one of the main factors that lead to the development of type 2 diabetes
mellitus (T2DM). The effect of alkaloids on insulin resistance has been extensively examined according
to multiple scientific researches.

Objective:
In this work, we aimed to summarize the interesting results from preclinical and clinical studies that
assessed the effects of natural alkaloids (berberine, nigelladine A, piperine, trigonelline, capsaicin, nuciferine,
evodiamine, mahanine, and magnoflorine) on impaired insulin sensitivity and worsened insulin resistance,
which play a pivotal role in the pathogenesis of type 2 diabetes.

Methods:
In the current review, PubMed, ScienceDirect, Springer, and Google Scholar databases were used.
The inclusion criteria were based on the following keywords and phrases: insulin sensitivity, insulin resistance,
alkaloids and insulin resistance, alkaloids and type 2 diabetes, mechanisms of action, and alkaloids.

Results:
The outcomes reported in this review demonstrated that the selected alkaloids increased insulin sensitivity
and reduced insulin resistance in vitro and in vivo evidence, as well as in clinical trials, through improving
insulin-signaling transduction mainly in hepatocytes, myocytes, and adipocytes, both at cellular and molecular
levels. Insulin signaling components (InsR, IRS-1, PI3K, Akt, etc.), protein kinases and phosphatases, receptors,
ion channels, cytokines, adipokines, and microRNAs, are influenced by alkaloids at transcriptional
and translational levels, also in terms of function (activity and/or phosphorylation). Multiple perturbations associated
with insulin resistance, such as ectopic lipid accumulation, inflammation, ER stress, oxidative stress,
mitochondrial dysfunction, gut microbiota dysbiosis, and β-cell failure, are reversed after treatment with alkaloids.
Furthermore, various indices and tests are employed to assess insulin resistance, including the Matsuda
index, insulin sensitivity index (ISI), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT),
which are all enhanced by alkaloids. These improvements extend to fasting blood glucose, fasting insulin, and
HbA1c levels as well. Additionally, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
and the Homeostasis Model Assessment of β-cell function (HOMA-β) are recognized as robust markers of insulin
sensitivity and β-cell function, and it is noteworthy that alkaloids also lead to improvements in these two
markers.

Conclusion:
Based on the findings of the current review, alkaloids may serve as both preventive and curative
agents for metabolic disorders, specifically type 2 diabetes. Nonetheless, there is an urgent need for additional
clinical trials to explore the potential benefits of alkaloids in both healthy individuals and those with type 2 diabetes.
Additionally, it is crucial to assess any possible side effects and interactions with antidiabetic drugs.
Design, Synthesis, and in vitro Evaluation of Derivatives of Quinoxaline-2-
One as a Myeloperoxidase Modulator Using in silico Methods
Authors: Parameswaran Dakshinesh , Thangavelu Saravanan , Selvaraj Jubie , Chellappa Selvinthanuja , Vivekanandan Lalitha , Veerasamy Ravichandran , Thangavelu Prabha 
Published: December 2023

Background:
In some pathological situations, the overproduction of oxidising agents
also results in oxidative damage to host cell proteins and DNA, which induces abnormal expression
of inflammatory cytokines and chemokines. A recently discovered biomarker of inflammation
is myeloperoxidase. Various inflammatory conditions cause the release of this enzyme into
the extracellular environment.

Objective:
Our study aimed to design, synthesize, and in vitro evaluate derivatives of quinoxaline-
2-one as a myeloperoxidase modulator using in silico methods.

Methods:
A series of quinoxaline-2-one derivatives was synthesized and characterized by
various analytical techniques. Further, to confirm and explore the molecular mechanism,
an in silico docking study against the myeloperoxidase enzyme was performed (PDB ID:
1DNU).

Results:
The compounds Q1, Q2, and Q5 showed better antioxidant activity in the DPPH assay,
whereas the nitric oxide scavenging assay showed the compounds Q2, Q4, and Q5 had significant
activity when compared to the standard IC50 value (28.8 μg/ml). Besides, the anti-inflammatory
studies showed the compounds Q1, Q3, and Q5 had better inhibition (89.79%) when compared to
the standard drug aceclofenac (85.37%) at 1000 μg/ml concentration. The top three ligands for
myeloperoxidase (PDB ID: 1DNU) with the highest scores in activity were found as Q2, Q1, and
Q5, with scores of -13.2838, -12.5841, and -11.6906 Kcal/mol, respectively. The compounds
were efficiently bound to the myeloperoxidase active site with arene-arene, arene-cation, and
hydrogen bonding interactions.

Conclusion:
By introducing the various heterocyclic rings and deactivating and activating
groups, we may produce a newer class of candidates for many infectious diseases. Thus, from the
computational studies carried out, we may obtain hints for optimising the molecular selectivity of
the quinoxaline-2-one derivatives to provide help in the design of new compounds for effective
myeloperoxidase enzyme modulators. However, further pharmacokinetics, pharmacodynamics,
preclinical, and clinical studies permit the design of the new agents without undesirable interactions.
Compression Promotes the Osteogenic Differentiation of Human
Periodontal Ligament Stem Cells by Regulating METTL14-mediated
IGF1
Authors: Wu Zengbo 
Published: December 2023

Background and Objectives::
Orthodontic treatment involves the application of mechanical
force to induce periodontal tissue remodeling and ultimately promote tooth movement. It is essential
to study the response mechanisms of human periodontal ligament stem cells (hPDLSCs) to
improve orthodontic treatment.

Methods::
In this study, hPDLSCs treated with compressive force were used to simulate orthodontic
treatment. Cell viability and cell death were assessed using the CCK-8 assay and TUNEL staining.
Alkaline phosphatase (ALP) and alizarin red staining were performed to evaluate osteogenic
differentiation. The binding relationship between IGF1 and METTL14 was assessed using RIP
and dual-luciferase reporter assays.

Results::
The compressive force treatment promoted the viability and osteogenic differentiation of
hPDLSCs. Additionally, m6A and METTL14 levels in hPDLSCs increased after compressive
force treatment, whereas METTL14 knockdown decreased cell viability and inhibited the osteogenic
differentiation of hPDLSCs treated with compressive force. Furthermore, the upregulation
of METTL14 increased m6A levels, mRNA stability, and IGF1 expression. RIP and dual-luciferase
reporter assays confirmed the interaction between METTL14 and IGF1. Furthermore, rescue
experiments demonstrated that IGF1 overexpression reversed the effects of METTL14 knockdown
in hPDLSCs treated with compressive force.

Conclusions::
In conclusion, this study demonstrated that compressive force promotes cell viability
and osteogenic differentiation of hPDLSCs by regulating IGF1 levels mediated by METTL14.
Novel Anti-tumor Strategy for Breast Cancer: Synergistic Role of Oleuropein with
Paclitaxel Therapeutic in MCF-7 Cells
Authors: Yılmaz Gamze , Özdemir Filiz 
Published: December 2023

Background:
The side effects of conventional therapeutics pose a problem for cancer treatment. Recently, combination treatments with natural compounds have attracted attention regarding limiting the side effects
of treatment. Oleuropein is a natural polyphenol in olives that has antioxidant and anticancer effects

Objective:
This study aimed to investigate the oxidative stress effect of a combination of Paclitaxel, a chemotherapeutic agent, and Oleuropein in the MCF-7 cell line.

Method:
The xCELLigence RTCA method was used to determine the cytotoxic effects of Oleuropein and
Paclitaxel in the MCF-7 cell line. The Total Oxidant and Total Antioxidant Status were analyzed using a kit. The
Oxidative Stress Index was calculated by measuring Total Oxidant and Total Antioxidant states. The levels of
superoxide dismutase, reduced glutathione and malondialdehyde, which are oxidative stress markers, were also
measured by ELISA assay kit.

Results:
As a result of the measurement, IC50 doses of Oleuropein and Paclitaxel were determined as 230 µM and
7.5 µM, respectively. Different percentages of combination ratios were generated from the obtained IC50 values.
The effect of oxidative stress was investigated at the combination rates of 10%, 20%, 30%, and 40% which were
determined to be synergistic. In terms of the combined use of Oleuropein and Paclitaxel on oxidative stress, antioxidant defense increased, and Oxidative Stress Index levels decreased.

Conclusion:
These findings demonstrate that the doses administered to the Oleuropein+Paclitaxel combination
group were lower than those administered to groups using one agent alone (e.g. Paclitaxel), the results of which
reduce the possibility of administering toxic doses.
Protective Effect of Hydroalcoholic Extract of Punica granatum Leaves on
High Fructose Induced Insulin Resistance in Experimental Animals
Authors: Bandawane Deepti , Kotkar Ashwini , Ingole Pooja 
Published: December 2023

Background::
Insulin resistance (IR) is a condition characterized by reduced sensitivity
of body tissues to insulin, leading to impaired regulation of downstream metabolic pathways
and elevated blood glucose levels. Diets rich in fructose have been proven to cause insulin resistance
in test rats, resulting in decreased insulin sensitivity, particularly in the liver, and compromised
disposal of glucose from the body. In the search for effective treatments, Plant-derived
formulations have gained popularity because to their ability for treating a variety of ailments.
One such plant is Punica granatum Linn. from the Punicaceae family, which has long been used
in the treatment of diabetes and its consequences. This study investigates the insulin-resistant
activity of an extract from Punica granatum leaves. The study goal is to assess the possible protective
role of Punica granatum against insulin resistance through various analyses, including
serum glucose and insulin levels, lipid profile assessment, measurement of liver enzymes (ALP,
SGOT, SGPT), and histopathological examination of liver sections.

Methods::
The study involves several key methods to evaluate the insulin-resistant activity of
Punica granatum extract in high fructose diet induced insulin resistance animal model. The extract
was administered orally to the experimental animals. These methods include the measurement
of serum glucose and serum insulin levels, analysis of the lipid profile, quantification of
liver enzymes such as ALP, SGOT, and SGPT, and a detailed histopathological examination of
liver tissue sections. These analyses collectively provide insights into the impact of Punica
granatum extract on insulin resistance and related metabolic parameters.

Results::
Findings of this study provide insight on the possible benefits of Punica granatum extract
on insulin resistance. Through the assessment of serum glucose and insulin levels, lipid profile
analysis, and measurement of liver enzymes, the study elucidates the impact of the extract on
key metabolic indicators. Additionally, the histopathological examination of liver sections provides
visual insights into the structural changes that may occur as a result of the treatment.

Conclusion::
In conclusion, this study highlights the ability of Punica granatum extract as a candidate
for addressing insulin resistance. The findings suggest that the extract may have a protective
role against insulin resistance, as evidenced by improvements in serum glucose and insulin
levels, lipid profile, liver enzyme levels, and histopathological characteristics. Further research
and investigations are warranted to fully understand the mechanisms underlying these observed
effects and to validate the potential of Punica granatum extract as a therapeutic option for managing
insulin resistance and its associated complications.
Recent Developments in Drug Targets and Combination Therapy for the
Clinical Management of Hypertension
Authors: Niranjan Pradeep Kumar , Bahadur Shiv 
Published: December 2023

Abstract:
Raised blood pressure is the most common complication worldwide that may lead to
atherosclerosis and ischemic heart disease. Unhealthy lifestyles, smoking, alcohol consumption,
junk food, and genetic disorders are some of the causes of hypertension. To treat this condition,
numerous antihypertensive medications are available, either alone or in combination, that work
via various mechanisms of action. Combinational therapy provides a certain advantage over
monotherapy in the sense that it acts in multi mechanism mode and minimal drug amount is required
to elicit the desired therapeutic effect. Such therapy is given to patients with systolic
blood pressure greater than 20 mmHg and/or diastolic blood pressure exceeding 10 mmHg beyond
the normal range, as well as those suffering from severe cardiovascular disease. The selection
of antihypertensive medications, such as calcium channel blockers, angiotensin-converting
enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and low-dose diuretics, hinges
on their ability to manage blood pressure effectively and reduce cardiovascular disease risks.
This review provides insights into the diverse monotherapy and combination therapy approaches
used for elevated blood pressure management. In addition, it offers an analysis of combination
therapy versus monotherapy and discusses the current status of these therapies, from researchbased
findings to clinical trials.
Insights Into the Role of Copper in Neurodegenerative Diseases and the Therapeutic Potential of Natural Compounds
Authors: Zhong Guangcheng , Wang Xinyue , Li Jiaqi , Xie Zhouyuan , Wu Qiqing , Chen Jiaxin , Wang Yiyun , Chen Ziying , Cao Xinyue , Li Tianyao , Liu Jinman , Wang Qi 
Published: December 2023

Abstract:Neurodegenerative diseases encompass a collection of neurological disorders originating from the progressive degeneration of neurons, resulting in the dysfunction of neurons. Unfortunately, effective therapeutic interventions for these diseases are presently lacking. Copper (Cu), a crucial trace element within the human body, assumes a pivotal role in various biological metabolic processes, including energy metabolism, antioxidant defense, and neurotransmission. These processes are vital for the sustenance, growth, and development of organisms. Mounting evidence suggests that disrupted copper homeostasis contributes to numerous age-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Wilson's disease (WD), Menkes disease (MD), prion diseases, and multiple sclerosis (MS). This comprehensive review investigates the connection between the imbalance of copper homeostasis and neurodegenerative diseases, summarizing pertinent drugs and therapies that ameliorate neuropathological changes, motor deficits, and cognitive impairments in these conditions through the modulation of copper metabolism. These interventions include Metal-Protein Attenuating Compounds (MPACs), copper chelators, copper supplements, and zinc salts. Moreover, this review highlights the potential of active compounds derived from natural plant medicines to enhance neurodegenerative disease outcomes by regulating copper homeostasis. Among these compounds, polyphenols are particularly abundant. Consequently, this review holds significant implications for the future development of innovative drugs targeting the treatment of neurodegenerative diseases.
Synthesis and Characterization of Nanomaterials from Porang (Amorphophallus muelleri) and Its Application for Bioplastic: Preliminary
Authors: Fadhallah Esa Ghanim , Indraningtyas Lathifa , Setiawan Teguh , Firdaus Iqbal , Pratama Andri 
Published: December 2023

The increase in plastic waste caused by population growth and human activities is capable of leading to negative consequences for the environment. The substantial accumulation contributes to environmental pollution since its resilience against microbial degradation poses a significant challenge. Furthermore, the utilization of bioplastics as a biodegradable substitute presents a viable strategy for diminishing reliance on synthetic plastics. Starch emerges as a prevalent primary component in the fabrication of bioplastics, owing to its array of merits including renewability, cost-effectiveness, non-toxicity, and facile degradability. The application of nanomaterials to bioplastics is believed to accelerate the degradation of bioplastics. Therefore, this study aimed to identify the characteristics of nanomaterial from porang (Amorphophallus muelleri) and bioplastic. The method included the extraction of porang nanomaterial through a specified water-to-porang ratio (2.5:1) followed by sonication (50 W, 75 minutes). The formulation of bioplastics involved the amalgamation of corn starch, porang nanomaterial, and glycerol. In addition, the chemical properties of porang nanomaterials included 41.41% starch content, 13.49% amylose, 7.87% ash, and 2.52% calcium oxalate. The particle size of porang nanomaterials was distributed from 603.7-952.1 nm with an average 722.6 nm crystalline structure containing calcium oxalate. The bioplastic had the form of a thin brown layer with a thickness value ranging from 0.23-0.39 mm. This research was expected to provide new information related to the essential characteristics of nanomaterials from porang and its potential application in solving environmental issues caused by synthetic plastics.
Penerimaan remaja putri terhadap tablet tambah darah di Kota Yogyakarta
Authors: Masfufah Masfufah , Kandarina Istiti , Padmawati Retna Siwi 
Published: December 2023

Acceptance of adolescent girls on iron tablets in Yogyakarta, IndonesiaBackground: Supplementation of iron tablets is one of the efforts to combat anemia in adolescent girls taken by the government. However, compliance with iron tablet consumption still tends to be low. Objective: This study aims to determine the acceptance of adolescent girls to iron tablets in Yogyakarta. Methods: This study is a sequential explanatory mixed method. The investigation was conducted from January to April 2018. The subjects of the study were girls in junior high and high school of Yogyakarta, as many as 211 people with criteria 12-18 years; FGD/in-depth interview respondents were 32 students, four teachers/UKS officer, two Puskesmas officers, and one health program holder. Results: Of 204 subjects who received iron tablets, only 133 subjects (65.20%) consumed iron tablets, and 71 subjects (34.80%) did not. The organoleptic perception of subjects consisting of flavor, aroma, and color indicates they like iron tablets, but some also do not want them because they smell fishy. Side effects of iron tablets, such as nausea, heartburn, constipation, and dizziness, are the reasons the subject does not consume or spend the iron tablets given. In addition to the encouragement or support of parents, teachers or officers of UKS, and health workers, it is a factor that affects the acceptance of subjects against iron tablets. Conclusion: Factors influencing the acceptance of adolescent girls to iron tablets are a factor in self and factors from outside (parents, teachers, and health workers). Therefore, increasing the consumption of iron tablets requires young women's self-awareness, motivation, and support from various parties to obtain information related to the iron tablet, such as socialization
Korelasi indeks massa tubuh terhadap rasio trigliserida dan high-density lipoprotein-cholesterol pada wanita usia subur dengan obesitas
Authors: Nasruddin Nina Indriyani , Saimin Juminten , Tosepu Ramadhan 
Published: December 2023

Body mass index correlation with triglyceride and high-density lipoprotein-cholesterol ratio of reproductive age women with obesityBackground: Obesity in women of reproductive age is thought to be one of the triggers of coronary heart disease. Body mass index (BMI) correlates well with the percentage of body fat, which is a strong indicator of coronary heart disease. Accumulation of visceral adipocytes releases excess free fatty acids, resulting in increased triglyceride synthesis. Furthermore, in a state of hypertriglyceridemia, there is a decrease in HDL levels and an increase in HDL catabolism resulting in decreased HDL levels. Examination of the ratio of triglyceride levels and high-density lipoprotein cholesterol (TG/HDL-C) is a strong indicator of cardiovascular disease.Objective: The aim of his study was to investigate the correlation between BMI and TG/HDL-C ratio in women of reproductive age.Methods: Using an analytical approach with a cross-sectional design. Furthermore, height and weight were measured with Smic ZT 120. At the same time as this examination, venous blood was taken from the median cubital area to be used to check the level of triglycerides and HDL-C in the serum. TG examination with GPO-PAP and HDL-C direct method. The bivariate analysis uses the Spearman Rank correlation test, while the multivariate analysis uses the linear regression test.Results: TG levels were 106 (34-363) mg/dl, HDL-C levels were 48.19 ± 9.91 mg/dl, and the ratio between the two was 2.26 (0.52-9.58). Spearman Rank analysis obtained the value of r was 0.573, p-value 0.0001.Conclusions: There is a significant positive correlation between BMI and the ratio of TG/HDL-C levels in adult women of reproductive age with obesity.
Usia ibu dan jumlah anak berhubungan dengan kejadian beban gizi ganda pada tingkat rumah tangga di desa dan kota di Indonesia
Authors: Astuti Nur Fitri Widya , Huriyati Emy , Susetyowati Susetyowati 
Published: December 2023

Maternal age and number of children are associated with the incidence of a double burden of malnutrition at the household level in rural and urban areas in IndonesiaBackground: Double burden of malnutrition is a nutritional problem where two nutritional problems occur at the same time and this can happen at the household level. The diversity of community characteristics causes differences in the incidence of the double burden of malnutrition at the household level in people living in rural and urban areas in Indonesia.Objective: To determine the associated factors with the incidence of double burden malnutrition at the household level in rural and urban areas in Indonesia.Methods: This study with a cross-sectional design used secondary data from the fifth wave of the Indonesia Family Life Survey (IFLS). The sample in this study was 6,468 households. The double burden of malnutrition at the household level is defined as a household in which there is at least one pair of mother and child aged 2-18 years that has underweight and or overweight/obese. Maternal factors, household economic status, number of children, and regional area are independent variables in this study. A logistic regression test was used to perform statistical analysis.Results: The prevalence of double burden malnutrition at the household level in urban areas was higher than in rural areas (8.70%) and 7.77%). Factors that were significantly (p<0.05) associated with the incidence of double burden malnutrition at the household level in rural areas were maternal age, mother's education, economic level, number of children, and regional living of the household, while in urban areas were maternal age and number of children.Conclusions: Maternal age and the number of children are two significant factors associated with the incidence of double burden malnutrition at the household level in rural and urban areas in Indonesia.