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1.
Cureus ; 16(6): e62468, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39015860

ABSTRACT

BACKGROUND: Significant links between low serum levels of vitamin D3 and insufficient glycemic control in patients with type 2 diabetes mellitus (T2DM) have been reported previously in the literature. However, there is no exciting evidence on the association between glycated hemoglobin (HbA1c) and vitamin D levels in T2DM individuals in our nation (Yemen). This study aimed to investigate the relationship between HbA1c and vitamin D levels in T2DM patients in a resource-limited setting. METHOD: A retrospective cross-sectional study was conducted at the Al-Raffa Center, Ibb, Yemen between June 2018 and September 2023 including 396 patients diagnosed with T2DM. The patient characteristics, comorbidities, HbA1c, and vitamin D levels were gathered from patients' medical profiles. Linear regression analysis was used to find the factors associated with vitamin D deficiency (serum 25(OH)D levels < 20 ng/mL) among T2DM patients. Subsequently, the correlation between HbA1c and vitamin D levels was examined using receiver operating characteristic (ROC) curve analysis. RESULTS: The mean age was 44.6 ±14.6 years and most of them (n= 227, 57.3%) were female and from a rural area (n= 229, 57.8%). Comorbidities were hypertension, dyslipidemia disease, and cardiovascular disease in 176 (44.4%), 63 (15.9%), and 88 (22.2%) cases, respectively. The mean HbA1c was 8.1 ±2.5%. The mean vitamin D level was 26.9 ±16.5 ng/mL and low vitamin D was present in 260 (65.7%) (vitamin D deficiency in 160 (40.4%) and vitamin D insufficiency in 100 (25.3%) cases). In regression analysis, obesity (>30 kg/m2) (odds ratio (OR): 299.49; 95% confidence interval (CI): 72.66 - 1234.42, p <0.0001), higher HbA1c levels (OR: 1.61; 95% CI: 1.26 - 2.05, p =0.0001), and urban residence (OR: 23.98; 95% CI: 5.62 - 102.42, p <0.0001) were associated with vitamin D deficiency. There was a negative correlation between the vitamin D level and HbA1c which was statistically significant (correlation coefficient r: -0.5452; 95% CI: -0.6109 to -0.4720, p <0.0001). Using the ROC analysis, the serum vitamin D value of ≤18.42 ng/ml was the best cut-off point to predict hyperglycemia (area under the curve: 0.633, 95% CI: 0.672 to 0.770, sensitivity: 52%, specificity: 84.71 %, Yoden's index: 0.3671, p <0.001). Based on this cut-off, 39.4% of individuals (37.5% in the normoglycemic group and 90.9% in the hyperglycemic group) were vitamin D deficient. CONCLUSION: In this study, low vitamin D was common among T2DM patients, especially those with poor glycemic control. We observed a link between HbA1c levels, urban residency, and BMI with vitamin D deficiency in T2DM patients. The association was distinguished by low vitamin D levels and elevated HbA1c. Additionally, we found that the serum vitamin D value of ≤18.42 ng/ml was the best cut-off point to predict hyperglycemia in T2DM patients with moderate agreement. To manage their disease, patients with T2DM should take their medications as prescribed and live a healthy lifestyle. This will increase their overall health, especially their vitamin D levels.

2.
Sci Rep ; 14(1): 16504, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39019932

ABSTRACT

This article aims to suggest an improved estimator for estimation of population median using auxiliary information under simple random sampling. The expression for the bias and mean square error are obtained up to first order approximation. We determine the MLE of the optimal values of the describing scalars. The proficiency of the suggested estimator is evaluated in comparison to the preliminary estimators using the MSE threshold. The suggested estimators are compared numerically to the ones that are currently studied in this study. The performance and novelty of the estimators was evaluated using real data sets and a simulation study. To check the efficiency of estimators empirical and theoretical study has been studied. Based on numerical result it is to be noted that our suggested estimator is more efficient as compared to existing estimators which is considered in this article in terms of least MSE and greater PRE.

3.
J Fungi (Basel) ; 10(6)2024 May 24.
Article in English | MEDLINE | ID: mdl-38921363

ABSTRACT

In this study, bacteria residing in the gut of the rice weevils (Sitophilus oryzae L.) (Coleoptera: Curculionidae) feeding on aflatoxin-contaminated corn kernels were isolated and evaluated for their ability to suppress Aspergillus flavus and to remove/degrade aflatoxin B1 (AFB1). Four morphologically distinct S. oryzae gut-associated bacterial isolates were isolated and identified as Bacillus subtilis (RWGB1), Bacillus oceanisediminis (RWGB2), Bacillus firmus (RWGB3), and Pseudomonas aeruginosa (RWGB4) based on 16S rRNA gene sequence analysis. These bacterial isolates inhibited A. flavus growth in the dual culture assay and induced morphological deformities in the fungal hyphae, as confirmed by scanning electron microscopy. All four bacterial isolates were capable of removing AFB1 from the nutrient broth medium. In addition, culture supernatants of these bacterial isolates degraded AFB1, and the degradation of toxin molecules was confirmed by liquid chromatography-mass spectrometry. The bacterial isolates, B. subtilis RWGB1, B. oceanisediminis RWGB2, and P. aeruginosa RWGB4, were capable of producing antifungal volatile organic compounds that inhibited A. flavus growth. These results suggest that the bacterial isolates from S. oryzae gut have the potential to bind and/or degrade AFB1. Further research on their application in the food and feed industries could enhance the safety of food and feed production.

4.
Ann Pediatr Cardiol ; 17(1): 77-80, 2024.
Article in English | MEDLINE | ID: mdl-38933044

ABSTRACT

We describe our findings in a child with a vein of Galen malformation, in whom the right superior caval and the azygos veins drained into the roof of the morphologically left atrium. A persistent left superior caval vein drained into the morphologically right atrium through the coronary sinus. The additional presence of dual brachiocephalic veins permitted the deployment of a multifunctional ventricular septal defect occluder device to occlude the right superior caval vein, correcting the right-to-left shunt. This also prevented azygos venous drainage into the left atrium.

5.
Med Sci Monit ; 30: e944628, 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38909276

ABSTRACT

BACKGROUND Cephalometric radiography evaluates facial skeleton development and aids in diagnosis and treatment phases (pre and post) in orthodontics. This study aimed to compare digital cephalometric tracing using a smartphone application (App), a tablet-based platform, and manual tracing in 30 orthodontic patients. MATERIAL AND METHODS Thirty orthodontic pretreatment, criteria based, lateral cephalometric radiographs were analyzed/grouped for Steiner analysis parameters (5 skeletal, 3 dentals, 1 soft tissue) by 3 tracing methods [manual - group (Gp M), smartphone (Android - OS9) - Gp S, tablet (Apple - IOS13) - Gp T) after mandatory standardization/calibration. Measurements include 5 angular (SNA, SNB, ANB, SNMPA, SNOP), 3 linear U1NA, L1NB, U1L1, and 1 soft tissue (S line) (millimeters and degrees). Inter-examiner rating was determined using Dahlberg's test. After normality distribution testing (Shapiro-Wilk), data were analyzed using one-way analysis of variance (ANOVA) for group differences. Homogeneity of variance was verified using the Levene test. Differences were determined on probability value of (p≤0.05). RESULTS The results showed that Steiner's analysis parameters were similar in all groups with homogenous variances. Highest differences in mean values were found for L1NB, U1L1, and S line measurement, with higher values being observed in Gp S tracings. However, these differences were not statistically significant (p≤0.05). All parameters, irrespective of being measured in either degrees or millimeters, had means comparable to each other. CONCLUSIONS Smartphone and tablet-based applications produced tracings that were comparable and reliable when compared to conventional manual tracings. Standardization of images, processing, printing, and calibration of devices is important to achieve good results.


Subject(s)
Cephalometry , Mobile Applications , Smartphone , Humans , Cephalometry/methods , Male , Female , Adolescent , Computers, Handheld , Orthodontics/methods
6.
Plast Reconstr Surg Glob Open ; 12(6): e5890, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38859805

ABSTRACT

Celiac disease is an autoimmune disease that occurs due to gluten intolerance. The prevalence of breast cancer among celiac disease patients is the same as in the general population. It is of note that breast cancer is the most common type of cancer in women. Following mastectomy, these patients visit plastic surgeons for breast reconstruction. Based on various factors, autologous reconstruction using abdominal-based flaps is the best option. Patients with celiac disease have a high incidence of thromboembolic disorders, which may prevent plastic surgeons from doing breast reconstruction with free flaps. We present a case of a patient with celiac disease who underwent a free flap for breast reconstruction with an uneventful course after using our routine postoperative protocol. This case report highlights that patients with celiac disease cannot be denied the option of breast reconstruction with free flaps.

8.
PLoS Pathog ; 20(6): e1011883, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38838057

ABSTRACT

ATP-binding cassette (ABC) transport systems are crucial for bacteria to ensure sufficient uptake of nutrients that are not produced de novo or improve the energy balance. The cell surface of the pathobiont Streptococcus pneumoniae (pneumococcus) is decorated with a substantial array of ABC transporters, critically influencing nasopharyngeal colonization and invasive infections. Given the auxotrophic nature of pneumococci for certain amino acids, the Ami ABC transporter system, orchestrating oligopeptide uptake, becomes indispensable in host compartments lacking amino acids. The system comprises five exposed Oligopeptide Binding Proteins (OBPs) and four proteins building the ABC transporter channel. Here, we present a structural analysis of all the OBPs in this system. Multiple crystallographic structures, capturing both open and closed conformations along with complexes involving chemically synthesized peptides, have been solved at high resolution providing insights into the molecular basis of their diverse peptide specificities. Mass spectrometry analysis of oligopeptides demonstrates the unexpected remarkable promiscuity of some of these proteins when expressed in Escherichia coli, displaying affinity for a wide range of peptides. Finally, a model is proposed for the complete Ami transport system in complex with its various OBPs. We further disclosed, through in silico modelling, some essential structural changes facilitating oligopeptide transport into the cellular cytoplasm. Thus, the structural analysis of the Ami system provides valuable insights into the mechanism and specificity of oligopeptide binding by the different OBPs, shedding light on the intricacies of the uptake mechanism and the in vivo implications for this human pathogen.


Subject(s)
ATP-Binding Cassette Transporters , Bacterial Proteins , Oligopeptides , Streptococcus pneumoniae , Streptococcus pneumoniae/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Oligopeptides/metabolism , ATP-Binding Cassette Transporters/metabolism , ATP-Binding Cassette Transporters/chemistry , Crystallography, X-Ray , Models, Molecular , Lipoproteins
9.
Sci Rep ; 14(1): 13155, 2024 06 07.
Article in English | MEDLINE | ID: mdl-38849386

ABSTRACT

Hepatocellular carcinoma (HCC) stands as the most prevalent form of primary liver cancer, predominantly affecting patients with chronic liver diseases such as hepatitis B or C-induced cirrhosis. Diagnosis typically involves blood tests (assessing liver functions and HCC biomarkers), imaging procedures such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI), and liver biopsies requiring the removal of liver tissue for laboratory analysis. However, these diagnostic methods either entail lengthy lab processes, require expensive imaging equipment, or involve invasive techniques like liver biopsies. Hence, there exists a crucial need for rapid, cost-effective, and noninvasive techniques to characterize HCC, whether in serum or tissue samples. In this study, we developed a spiral sensor implemented on a printed circuit board (PCB) technology that utilizes impedance spectroscopy and applied it to 24 tissues and sera samples as proof of concept. This newly devised circuit has successfully characterized HCC and normal tissue and serum samples. Utilizing the distinct dielectric properties between HCC cells and serum samples versus the normal samples across a specific frequency range, the differentiation between normal and HCC samples is achieved. Moreover, the sensor effectively characterizes two HCC grades and distinguishes cirrhotic/non-cirrhotic samples from tissue specimens. In addition, the sensor distinguishes cirrhotic/non-cirrhotic samples from serum specimens. This pioneering study introduces Electrical Impedance Spectroscopy (EIS) spiral sensor for diagnosing HCC and liver cirrhosis in clinical serum-an innovative, low-cost, rapid (< 2 min), and precise PCB-based technology without elaborate sample preparation, offering a novel non-labeled screening approach for disease staging and liver conditions.


Subject(s)
Carcinoma, Hepatocellular , Dielectric Spectroscopy , Liver Neoplasms , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/pathology , Humans , Dielectric Spectroscopy/methods , Liver Neoplasms/diagnosis , Liver Neoplasms/blood , Liver Neoplasms/pathology , Liver/pathology , Biomarkers, Tumor/blood
10.
Heliyon ; 10(10): e31034, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38803875

ABSTRACT

Drawing inspiration from recent advancements in robust mean estimation within finite sampling theory, we introduce a novel dual-type class of mean estimators in a design-based framework. The dual-type class is based on quantile regression and is specifically designed to be effective in the presence of extreme observations. Significantly, it integrates the averages of both sampled observations and non-sampled observations of auxiliary variable. In the initial discussion of this class, it is presumed that the target variable is non-sensitive, signifying its relevance to subjects that respondents do not consider embarrassing when queried directly. In this standard setting, we present specific estimators within the class and determine their theoretical properties. The class's scope broadens to include scenarios where the target variable incorporates sensitive topics, giving rise to nonresponse rates and inaccurate reporting. To alleviate these errors, one can promote respondent cooperation by employing scrambled response methods that obscure the actual value of the sensitive variable. Accordingly, the article delves into discussions on additive methods. Subsequently, a numerical study is conducted using asymmetric data to evaluate the effectiveness of the dual-type class by comparing it with several existing estimators, both in the absence and presence of scrambled responses.

11.
Heliyon ; 10(10): e31030, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38803863

ABSTRACT

Recently, several memory-type mean estimators (including ratio, product, and logarithmic) have been developed. These estimators rely on exponentially weighted moving average (EWMA), which incorporate both historical and present sample data. In this article, we propose EWMA type calibrated estimators under single and double stratified random sampling (StRS). Because calibration method enhances the estimates by modifying the stratification weight, taking advantage of supplementary information. To evaluate the performance of estimators, various real-world time-scaled data sets pertaining to stock market and weather are taken into account. Additionally, we also conduct a simulation study using a bivariate symmetric data set. The numerical results show the superiority of proposed estimators (y¯TM,y¯TaM) over the adapted ones (y¯PM,y¯PaM).

12.
Heliyon ; 10(10): e31035, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38803969

ABSTRACT

Implementing Internet of things (IoT) technology in the context of intelligent buildings and infrastructure development has garnered significant attention within the construction sector. Nonetheless, the implementation of IoT could be improved by assessing various barriers. The purpose of this study was to examine the obstacles related to the adaptation of IoT techniques within the construction sector, as well as the effects on the advancement of intelligent building and infrastructure systems. The study employed a mixed-method approach involving exploratory factor analysis (EFA) and structural equation modeling (SEM) to determine six types of barriers: knowledge, technical, standardization, creativity, complexity, and economics. The study revealed that the implementation of IoT for developing smart construction and infrastructure in the construction sector was significantly influenced by all six constructs. The results of this study offer significant ramifications for the field. The study underscores the necessity for heightened consciousness and instruction regarding the advantages of implementing IoT. The study posits that the technical barriers, including interoperability, modernization of legacy infrastructure, and coordination and collaboration difficulties, require attention from the industry. The study highlights the significance of establishing industry-wide standards and protocols for implementing IoT and regulatory and legal frameworks. Finally, the study underscores the necessity for augmented funding and financing options for IoT endeavors. Subsequent study endeavors may expand upon the present findings by delving into the barriers encountered by alternative sectors and nations and assessing the efficacy of the suggested measures in this investigation.

13.
Children (Basel) ; 11(5)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38790509

ABSTRACT

BACKGROUND: The dreaded sensation of pain in the dental chair has a significant impact on children's behavior. This study aimed to compare and contrast the perception of pain and patient behavior between the use of INJEX and the conventional syringe needle technique during pulpotomy among children. METHODS: A randomized clinical trial was designed and conducted among pediatric dentistry patients aged 6-12 years old. Fifty-eight children were divided into two groups, conventional syringe needle and INJEX, using simple randomization method applying the sequentially numbered, opaque, sealed envelope method of allocation concealment. Anesthesia was administered to the groups as local infiltration by a single operator following routine behavior guidance techniques. After 3 min, pulpotomy was performed using the standard protocol. The Face, Legs, Activity, Cry, Consolability (FLACC) scale and Wong-Baker FACES Pain Rating Scale (WBS) were used to assess the intensity of pain, while the Frankl behavior rating scale (FBRS) was used to assess the children's behavior. RESULTS: During anesthesia, most of the participants in the INJEX group (median = 3) had higher FBRS scores compared with the conventional syringe needle group (median = 2), and the difference was very highly significant (p-value < 0.001). Analyzing the FLACC scores during local anesthesia administration revealed a high statistical significance (p-value < 0.01) across the two groups. A very high statistically significant difference (p-values < 0.001) with higher WBS scores for pain intensity was seen in the group using conventional syringe needles. CONCLUSIONS: INJEX administration significantly reduced the intensity of pain experienced by the children and helped maintain a positive attitude among them during pulpotomy. It provided a positive and comfortable experience for both the child and the practitioner. Therefore, it can serve as an excellent alternative to conventional needle anesthesia.

14.
Heliyon ; 10(7): e28327, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38571640

ABSTRACT

Survey sampling has wide range of applications in social and scientific investigation to draw inference about the unknown parameter of interest. In complex surveys, the sample information about the study variable cannot be expressed by a precise number under uncertain environment due fuzziness and indeterminacy. Therefore, this information is expressed by neutrosophic numbers rather than the classical numbers. The neutrosophic statistics, which is generalization of classical statistics, deals with the neutrosophic data that has some degree of indeterminacy and fuzziness. In this study, we investigate the compromise optimum allocation problem for estimating the population means of the neutrosophic study variables in a multi-character stratified random sampling under uncertain per unit measurement cost. We proposed the intuitionistic fuzzy cost function, modeling the fuzzy uncertainty in stratum per unit measurement cost. The compromise optimum allocation problem is formulated as a multi-objective intuitionistic fuzzy optimization problem. The solution methodology is suggested using neutrosophic fuzzy programming and intuitionistic fuzzy programming approaches. A numerical study includes the means estimation of atmospheric variables is presented to explore the real-life application, explain the mathematical formulation, and efficiency comparison with some existing methods. The results show that the suggested methods produce more precise estimates with less utilization of survey resources as compared to some existing methods. The Python is used for statistical analysis, graphical designing and numerical optimization problems are solved using GAMS.

15.
Heliyon ; 10(8): e29592, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38681596

ABSTRACT

The present work gives generalized form of the class of estimators if unit non-response is acquired in small domains. We have obtained indirect method like synthetic. It has provided specific instances where the proposed estimators are unbiased. It has also given a generalized form of the synthetic estimators. The four estimators were investigated with coefficient of variation and kurtosis constants. Because, these are obtained from the available variable. We conducted atheoretical comparison between traditional and proposed calibration estimators for estimating the domain totals. It found that the proposed estimators are more efficient than traditional estimators for investigate small domains.

16.
J Fungi (Basel) ; 10(4)2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38667955

ABSTRACT

Pythium-induced damping-off of cucumber is a major constraint to cucumber production in different parts of the world. Although chemical fungicides are used for managing this disease, they have many drawbacks to the environment. The ability of the antagonistic fungi isolated from the rhizosphere and endosphere of Dactyloctenium robecchii and Moraea sisyrinchium in the control of soilborne pathogen Pythium aphanidermatum was inspected. Native Trichoderma isolates, Trichoderma ghanense and Trichoderma citrinoviride, were isolated from plant stem and soil samples collected from Al-Seeb, Oman. Using a dual culture technique, the antagonistic activity of the fungal isolates against P. aphanidermatum was examined in vitro. Among Trichoderma isolates, T. ghanense was more efficient in restraining the mycelial growth of P. aphanidermatum, causing an inhibition percentage of 44.6%. Further, T. citrinoviride induced significantly lower cessation of P. aphanidermatum mycelial growth (31.3%). Microscopic and electrolyte leakage inspection of the pathogen mycelia depicted extreme morphological malformations in their mycelium, which can be attributed to the antifungal metabolites of antagonists. Greenhouse studies demonstrated the effectivity of T. ghanense in controlling Pythium damping-off of cucumber plants, where the number of surviving plants was over 90% when the biocontrol agents were used compared to 0 in the control plants. Furthermore, treatment of the plants with the antagonists promoted growth characteristics of plants compared to uninoculated plants. This included improvements in shoot and root lengths, leaf length and width, and dry weight. These findings suggest that T. ghanense and T. citrinoviride can be developed as alternatives to synthetic chemical fungicides to manage soilborne pathogens of cucumber. This research is also the first to clarify the biocontrol ability of T. citrinoviride and T. ghanense against cucumber damping-off caused by P. aphanidermatum.

17.
Front Pharmacol ; 15: 1358089, 2024.
Article in English | MEDLINE | ID: mdl-38650632

ABSTRACT

This study discusses the synthesis and use of a new library of spirooxindole-benzimidazole compounds as inhibitors of the signal transducer and activator of p53, a protein involved in regulating cell growth and cancer prevention. The text includes the scientific details of the [3 + 2] cycloaddition (32CA) reaction between azomethine ylide 7a and ethylene 3a within the framework of Molecular Electron Density Theory. The mechanism of the 32CA reaction proceeds through a two-stage one-step process, with emphasis on the highly asynchronous transition state structure. The anti-cancer properties of the synthesized compounds, particularly 6a and 6d, were evaluated. The inhibitory effects of these compounds on the growth of tumor cells (MDA-MB 231 and PC-3) were quantified using IC50 values. This study highlights activation of the p53 pathway by compounds 6a and 6d, leading to upregulation of p53 expression and downregulation of cyclin D and NF-κB in treated cells. Additionally, we explored the binding affinity of spirooxindole analogs, particularly compound 6d, to MDM2, a protein involved in regulation of p53. The binding mode and position of compound 6d were compared with those of a co-crystallized standard ligand, suggesting its potential as a lead compound for further preclinical research.

18.
Hand (N Y) ; : 15589447241247332, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38660977

ABSTRACT

BACKGROUND: ChatGPT, an artificial intelligence technology, has the potential to be a useful patient aid, though the accuracy and appropriateness of its responses and recommendations on common hand surgical pathologies and procedures must be understood. Comparing the sources referenced and characteristics of responses from ChatGPT and an established search engine (Google) on carpal tunnel surgery will allow for an understanding of the utility of ChatGPT for patient education. METHODS: A Google search of "carpal tunnel release surgery" was performed and "frequently asked questions (FAQs)" were recorded with their answer and source. ChatGPT was then asked to provide answers to the Google FAQs. The FAQs were compared, and answer content was compared using word count, readability analyses, and content source. RESULTS: There was 40% concordance among questions asked by the programs. Google answered each question with one source per answer, whereas ChatGPT's answers were created from two sources per answer. ChatGPT's answers were significantly longer than Google's and multiple readability analysis algorithms found ChatGPT responses to be statistically significantly more difficult to read and at a higher grade level than Google's. ChatGPT always recommended "contacting your surgeon." CONCLUSION: A comparison of ChatGPT's responses to Google's FAQ responses revealed that ChatGPT's answers were more in-depth, from multiple sources, and from a higher proportion of academic Web sites. However, ChatGPT answers were found to be more difficult to understand. Further study is needed to understand if the differences in the responses between programs correlate to a difference in patient comprehension.

19.
Front Chem ; 12: 1364378, 2024.
Article in English | MEDLINE | ID: mdl-38487783

ABSTRACT

Cancer represents a global challenge, and the pursuit of developing new cancer treatments that are potent, safe, less prone to drug resistance, and associated with fewer side effects poses a significant challenge in cancer research and drug discovery. Drawing inspiration from pyrrolidinyl-spirooxindole natural products, a novel series of spirooxindoles has been synthesized through a one-pot three-component reaction, involving a [3 + 2] cycloaddition reaction. The cytotoxicity against breast cancer cells (MCF-7 and MDA-MB-231) and safety profile against WISH cells of the newly developed library were assessed using the MTT assay. Compounds 5l and 5o exhibited notable cytotoxicity against MCF-7 cells (IC50 = 3.4 and 4.12 µM, respectively) and MDA-MB-231 cells (IC50 = 8.45 and 4.32 µM, respectively) compared to Erlotinib. Conversely, compounds 5a-f displayed promising cytotoxicity against MCF-7 cells with IC50 values range (IC50 = 5.87-18.5 µM) with selective activity against MDA-MB-231 cancer cells. Compound 5g demonstrated the highest cytotoxicity (IC50 = 2.8 µM) among the tested compounds. Additionally, compounds 5g, 5l, and 5n were found to be safe (non-cytotoxic) against WISH cells with higher IC50 values ranging from 39.33 to 47.2 µM. Compounds 5g, 5l, and 5n underwent testing for their inhibitory effects against EGFR and CDK-2. Remarkably, they demonstrated potent EGFR inhibition, with IC50 values of 0.026, 0.067, and 0.04 µM and inhibition percentages of 92.6%, 89.8%, and 91.2%, respectively, when compared to Erlotinib (IC50 = 0.03 µM, 95.4%). Furthermore, these compounds exhibited potent CDK-2 inhibition, with IC50 values of 0.301, 0.345, and 0.557 µM and inhibition percentages of 91.9%, 89.4%, and 88.7%, respectively, in contrast to Roscovitine (IC50 = 0.556 µM, 92.1%). RT-PCR analysis was performed on both untreated and 5g-treated MCF-7 cells to confirm apoptotic cell death. Treatment with 5g increased the gene expression of pro-apoptotic genes P53, Bax, caspases 3, 8, and 9 with notable fold changes while decreasing the expression of the anti-apoptotic gene Bcl-2. Molecular docking and dynamic simulations (100 ns simulation using AMBER22) were conducted to investigate the binding mode of the most potent candidates, namely, 5g, 5l, and 5n, within the active sites of EGFR and CDK-2.

20.
Heliyon ; 10(6): e27522, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38496881

ABSTRACT

Estimation of population mean is a determined subject issue in sampling surveys and many efforts have been paid by various researchers to enhance the precision of the estimates by utilizing the correlated auxiliary information. In connection with this, we suggest an improved exponential ratio-cum-ratio estimator using transformed auxiliary variables under ranked set sampling scheme. Theoretical comparison between estimators is made in terms of mean square errors (MSEs), percentage relative efficiencies (PREs), and percentage relative root mean squared error (PRRMSE). The numerical expression for the bias and MSE of the suggested estimator is derived up to first order of approximation. Based on the results of actual data sets and a simulation study, it is found that the suggested estimator perform well as compared to its existing counterparts.

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