Phase Of Cycle Research Articles

Correlation of sex hormone levels with orthodontic tooth movement in the maxilla: a prospective cohort study.

Sex hormones secreted during the menstrual cycle and the application of orthodontic forces to teeth can affect the metabolism of periodontal ligaments. This study aimed to determine whether there are any differences in orthodontic tooth displacement during the menstrual cycle and when using hormonal contraceptives and whether the amount of female sex hormones influences the efficiency of tooth displacement. A total of 120 women aged between 20 and 30 years with Angle Class II requiring transpalatal arch (TPA) to derotate teeth 16 and 26 were included in this study. The participants were divided into two groups: group A, which included women with regular menstruation, and control group B, which included women taking monophasic combined oral contraceptives. Group A was divided into subgroups according to the moment of TPA activation: menstruation (A1), ovulation phase (A2), and luteal phase (A3) (examination I). On intraoral scans, measurement points were marked on the proximal mesial cusps of teeth 16 and 26, and the intermolar distance (M1) was determined. The change in the position of the measurement points 6 weeks after activation (examination II) made it possible to determine the derotating extent of teeth 16 (O16) and 26 (O26) and the widening of the intermolar distance (M2-M1). In examinations I and II, tooth mobility in the alveoli was assessed using Periotest based on the periotest values (PTV) PTV1 and PTV2, respectively. A significant difference in all parameters was observed among groups A1, A2, and A3 (P < 0.001). Group A3 showed the highest values of parameters O16, O26, and M2-M1, and group A2 showed the lowest values, which did not differ from the control group (P = 0.64). PTV2 and PTV1 were the highest in group A3 and the lowest in groups A1 and B. Intergroup differences were statistically significant (P < 0.001). With the quantification of changes in tooth mobility in the alveoli during the menstrual cycle in women undergoing orthodontic treatment, it was possible to determine that female sex hormones affect the effectiveness of orthodontic treatment, and the optimal moment for TPA activation is the luteal phase of the menstrual cycle.

Privacy Challenges and Solutions in Big Data Analytics: A Comprehensive Review

Abstract: Large data collections with a more intricate and diversified structure are referred to as "big data." These traits are typically associated with more challenges when it comes to storing, analyzing, and applying additional procedures or getting results. The technique of analyzing vast quantities of intricate data to uncover patterns or connections that are concealed is known as "big data analytics." Nonetheless, there is a clear conflict between big data's extensive use and its security and privacy. This paper examines privacy needs in big data, distinguishes between privacy and security, and focuses on privacy and security issues in large data. This study addresses the applications of privacy in business by utilizing established techniques like HybrEx, k-anonymity, T-closeness, and L-diversity. Many privacy-preserving techniques have been created for protection of privacy at various phases of the big data life cycle (such as data generation, storage, and processing). This work aims to explain the issues facing current privacy preservation strategies in big data and to give a comprehensive evaluation of them. This study also introduces new approaches to privacy preservation in big data, such as quick anonymization of massive data streams, identity-based anonymization, differential privacy, privacy preserving big data publishing, and hiding a needle in a haystack. This study discusses big data privacy and security issues in healthcare. A comparative analysis of some contemporary large data privacy approaches is also conducted. A comparative analysis of the latest big data privacy approaches is also conducted.

Evaluation of mitral chordae tendineae length using four-dimensional computed tomography

BACKGROUND Mitral valvuloplasty using artificial chordae tendineae represents an effective surgical approach for treating mitral regurgitation. Achieving precise measurements of artificial chordae tendineae length (CL) is an important factor in the procedure; however, no objective index currently exists to facilitate this measurement. Therefore, preoperative assessment of CL is critical for surgical planning and support. Four-dimensional x-ray micro-computed tomography (4D-CT) may be useful for accurate CL measurement considering that it allows for dynamic three-dimensional (3D) evaluation compared to that with transthoracic echocardiography, a conventional inspection method. AIM To investigate the behavior and length of mitral chordae tendineae during systole using 4D-CT. METHODS Eleven adults aged &gt; 70 years without mitral valve disease were evaluated. A 64-slice CT scanner was used to capture 20 phases in the cardiac cycle in electrocardiographic synchronization. The length of the primary chordae tendineae was measured from early systole to early diastole using the 3D image. The primary chordae tendineae originating from the anterior papillary muscle and attached to the A1-2 region and those from the posterior papillary muscle and attached to the A2-3 region were designated as cA and cP, respectively. The behavior and maximum lengths [cA (ma), cP (max)] were compared, and the correlation with body surface area (BSA) was evaluated. RESULTS In all cases, the mitral anterior leaflet chordae tendineae could be measured. In most cases, the cA and cP chordae tendineae could be measured visually. The mean cA (max) and cP (max) were 20.2 mm ± 1.95 mm and 23.5 mm ± 4.06 mm, respectively. cP (max) was significantly longer. The correlation coefficients (r) with BSA were 0.60 and 0.78 for cA (max) and cP (max), respectively. Both cA and cP exhibited constant variation in CL during systole, with a maximum 1.16-fold increase in cA and a 1.23-fold increase in cP from early to mid-systole. For cP, CL reached a plateau at 15% and remained elongated until end-systole, whereas for cA, after peaking at 15%, CL shortened slightly and then moved toward its peak again as end-systole approached. CONCLUSION The study suggests that 4D-CT is a valuable tool for accurate measurement of both the length and behavior of chordae tendineae within the anterior leaflet of the mitral valve.

Habitat type modulates sharp body mass oscillations in cyclic common vole populations

Cyclic rodent populations exhibit pronounced changes in body mass associated with the population cycle phase, long-known as Chitty effect. Although Chitty effect is a common epiphenomenon in both America and Europe, there is still incomplete evidence about the generality of these patterns across the entire range of most species. Moreover, despite decades of research, the underlying factors driving Chitty effect remains poorly understood. Here, we examined the influence of intrinsic and extrinsic factors that may underlie observed patterns in vole size variation in the Iberian common vole Microtus arvalis asturianus. We weighed and measured 2816 adult voles that were captured during 6 trapping periods. Vole numbers and body mass showed strong period- and phase-related variation both in females and males, demonstrating marked Chitty effect in the studied population. Body mass of adult males correlated with body length, evidencing that heavier males are also structurally larger. Statistical models showed that probability of occurrence of large-sized vole (> 37 g) was significantly more likely in reproductive males, during increase and peak phases, and it was modulated by habitat, with crop fields and field margins between crops showing an increased likelihood. We suggest an effect of the habitat on vole body mass mediated by predation.

Sleep characteristics in underweight young females across their menstrual cycles: A sleep-monitoring survey study with preliminary results.

This study investigated the association between underweight and sleep in young females across their menstrual cycles. A lifestyle-monitoring survey was conducted among 38 female university students aged 18-24 years in Japan from January to December 2023. Sleep data from 28 participants were analysed. Participants were categorized into underweight (n = 10) and control (n = 18) groups based on a baseline body mass index cut-off of 18.5 kg m-2. Sleep parameters were assessed using a daily sleep questionnaire, sleep sensor mats, and urinary melatonin metabolites across their menstrual cycles. The results indicated no significant differences in sleep patterns between the underweight and control groups or menstrual cycle phases, as assessed using both the daily sleep questionnaire and the sleep sensor mats. However, underweight participants experienced more difficulty maintaining sleep during the follicular phase. Body mass index significantly correlated with sleep efficiency (rs = 0.52) and wake after sleep onset (rs = -0.56). While urinary melatonin metabolite levels did not differ significantly between the groups or menstrual cycle phases, decreased levels during the luteal phase were more prevalent in the underweight group (7 of 10 participants) than in the control group (3 of 13 participants). This study suggests an association between underweight and sleep quality, especially nocturnal awakening, in young females. These findings underscore the importance of considering sleep quality in the management of underweight young females to improve their overall health outcomes.

Innovating in the Detection of Depression in Young Adults: Development of a Mobile Application Based on the Enhanced Cascade Model

Depression is a disorder that usually begins in early adulthood, having a duration according to the World Health Organization (WHO) from a couple of months to a couple of years, however, in approximately 20% of cases there is a chronic evolution that results in a high mortality rate by suicide due to lack of adequate treatment. Therefore, the objective of this project is to facilitate the tools for an adequate care of depression, mainly in young adults through the development of a mobile application that monitors patients. To carry out the project, the enhanced cascade model was implemented, because the feedback between the different phases of the system development life cycle is important to make the appropriate modifications. The application of interviews and the use of brainstorming were the selected way in which all the system requirements were designed and the goals to be met by the system were adequately defined.

Increased risk of supraventricular tachycardia with polycystic ovarian syndrome

Abstract Background Many arrhythmias are known to be triggered by hormonal imbalances. Polycystic ovarian syndrome (PCOS) is a common hormonal imbalance seen in reproductive aged women. There is sparse literature linking PCOS to increased risk of atrial fibrillation (1). We hypothesise that PCOS could also be associated with Supraventricular tachycardia (SVT) Purpose To determine if PCOS is a risk factor for SVT and Atrial fibrillation/flutter (AF/AFL). Methods Utilising the National Inpatient Sample (NIS) of the years 2015-2020, We performed a multivariable logistic regression analysis to determine if PCOS was independently associated with SVT and AF/AFL. The NIS is the largest publicly available database of United States containing data on upto 7 million hospital visits per year. Results From the years 2015 to 2020, PCOS was present in 367,375 adult patients and SVT was observed in 965, 799 patients. After adjusting for relevant risk factors, PCOS was associated with increased odds of SVT (OR 1.23, 95% CI 1.12-1.36, P&amp;lt;0.001) (Table 1). However, PCOS was not associated with increased odds of atrial fibrillation and atrial flutter (OR 0.72, 95% CI 0.66-0.77, P&amp;lt;0.001) Conclusion SVTs have been clinically observed to be more frequent in the luteal phase of the menstrual cycle due to low estrogen. The high androgen/estrogen ratio seen in PCOS may result in a similar increased risk of SVT in PCOS patients. PCOS is known to increase P wave maximum duration and dispersion, indicating abnormal atrial conduction (2). The negative association between AF/AFL is likely because PCOS is seen more commonly in younger patients, and AF/AFL is a disease of older adults. We recommend further studies in PCOS women to confirm our findings and characterise the mechanisms of SVT.

Household debt and financial vulnerability: empirical evidence for Spain, 2002–2020

AbstractThe aim of this paper is to analyse the evolution of Spanish households’ indebtedness and financial vulnerability over the course of this century using micro-data from the Household Finance and Consumption Survey. Our results show a growing debt participation of Spanish households and an increase in the stock of outstanding debt of indebted households, a trend that reversed with the end of the Great Recession. Moreover, the percentage of financially vulnerable households according to three indicators grew dramatically until the end of the downward phase of the last economic cycle and showed considerable signs of improvement during the second half of 2010s. These results, nonetheless, call attention to the number of Spanish households being unable to service their debts in the face of an economic downturn.

The Effect of Proprioceptive Insoles on Gait Kinematics in Healthy Participants

ABSTRACT Introduction Proprioceptive neuromuscular stimulating insoles (PNIs) enhance somatosensory information from the plantar region, thus modifying standing posture, balance, and ambulatory function. The present study investigated the short-term effects of customized PNIs on lower-limb kinematics during human locomotion. Materials and Methods Fifteen able-bodied volunteers were recruited and first examined with clinical evaluation of postural and feet behavior. Subjects performed 3-dimensional gait analysis (GA) while walking at self-selected speed in three different conditions: baseline, subjects barefoot; placebo, subjects wearing neutral insoles; and proprioceptive, subjects wearing PNIs. Spatiotemporal and kinematics data of the main lower-limb joints were acquired through a system of six photogrammetric infrared cameras acquiring at a sampling frequency of 100 Hz. Then, acquired parameters were compared in the three different conditions. Results We found a significant difference in the percentage of double-support phase (P = 0.022) and in ankle plantarflexion values during the toe-off phase of gait cycle (P = 0.022) between the three conditions. Post hoc analysis revealed that subjects wearing PNIs presented a significant reduction in percentage of double-support phase (P = 0.009) and reduced values of ankle plantarflexion during the toe-off phase of gait cycle (P = 0.02), compared with subjects in placebo condition. Conclusions Results suggest that proprioceptive insoles may induce modifications of gait biomechanics in able-bodied subjects, thus modulating movement strategies during human locomotion. Clinical Relevance These findings provide a basis for future investigation of the efficacy of these foot devices in a long-term period in able-bodied individuals and potentially in subjects with neurological impairment.

Variation in the Cost of Hip Arthroscopy for Labral Pathological Conditions: A Time-Driven Activity-Based Costing Analysis.

Despite growing interest in delivering high-value orthopaedic care, the costs associated with hip arthroscopy remain poorly understood. By employing time-driven activity-based costing (TDABC), we aimed to characterize the cost composition of hip arthroscopy for labral pathological conditions and to identify factors that drive variation in cost. Using TDABC, we measured the costs of 890 outpatient hip arthroscopy procedures for labral pathological conditions across 5 surgeons at 4 surgery centers from 2015 to 2022. All patients were ≥18 years old and were treated by surgeons who each performed ≥20 surgeries during the study period. Costs were normalized to protect the confidentiality of internal hospital cost data. Descriptive analyses and multivariable linear regression were performed to identify factors underlying cost variation. The study sample consisted of 515 women (57.9%) and 375 men (42.1%), with a mean age (and standard deviation) of 37.1 ± 12.7 years. Most of the procedures were performed in patients who were White (90.6%) or not Hispanic (93.4%). The normalized total cost of hip arthroscopy per procedure ranged from 43.4 to 203.7 (mean, 100 ± 24.2). Of the 3 phases of the care cycle, the intraoperative phase was identified as the largest generator of cost (>90%). On average, supply costs accounted for 48.8% of total costs, whereas labor costs accounted for 51.2%. A 2.5-fold variation between the 10th and 90th percentiles for total cost was attributed to supplies, which was greater than the 1.8-fold variation attributed to labor. Variation in total costs was most effectively explained by the labral management method (partial R2 = 0.332), operating surgeon (partial R2 = 0.326), osteoplasty type (partial R2 = 0.087), and surgery center (partial R2 = 0.086). Male gender (p < 0.001) and younger age (p = 0.032) were also associated with significantly increased costs. Finally, data trends revealed a shift toward labral preservation techniques over debridement during the study period (with the rate of such techniques increasing from 77.8% to 93.2%; Ptrend = 0.0039) and a strong correlation between later operative year and increased supply costs, labor costs, and operative time (p < 0.001 for each). By applying TDABC to outpatient hip arthroscopy, we identified wide patient-to-patient cost variation that was most effectively explained by the method of labral management, the operating surgeon, the osteoplasty type, and the surgery center. Given current procedural coding trends, declining reimbursements, and rising health-care costs, these insights may enable stakeholders to design bundled payment structures that better align reimbursements with costs. Economic and Decision Analysis Level IV. See Instructions for Authors for a complete description of levels of evidence.

Primate-Specific DAZ Regulates Translation of Cell Proliferation-Related mRNAs and is Essential for Maintenance of Spermatogonia.

Primate-specific DAZ (deleted in azoospermia) has evolved in the azoospermia factor c (AZFc) locus on the Y chromosome. Loss of DAZ is associated with azoospermia in patients with deletion of the AZFc region (AZFc_del). However, the molecular mechanisms of DAZ in spermatogenesis remain uncertain. In this study, the molecular mechanism of DAZ is identified, which is unknown since it is identified 40 years ago because of the lack of a suitable model. Using clinical samples and cell models, it is shown that DAZ plays an important role in spermatogenesis and that loss of DAZ is associated with defective proliferation of c-KIT-positive spermatogonia in patients with AZFc_del. Mechanistically, it is shown that knockdown of DAZ significantly downregulated global translation and subsequently decreased cell proliferation. Furthermore, DAZ interacted with PABPC1 via the DAZ repeat domain to regulate global translation. DAZ targeted mRNAs that are involved in cell proliferation and cell cycle phase transition. These findings indicate that DAZ is a master translational regulator and essential for the maintenance of spermatogonia. Loss of DAZ may result in defective proliferation of c-KIT-positive spermatogonia and spermatogenic failure.

Подходы к построению трейсера бизнес-циклов на примере обрабатывающей промышленности России

The importance of studying business cycles is determined by the scale of their impact on the economy and society, which leads to the need to develop methods to counteract their negative impact. Given the complexity of the topic and the many theories and debates in the field, there is a need for a simple tool to present business cycle information in an intuitive way for a wide audience. Such a tool is a business cycle tracer. This article is devoted to testing the possibility of using three approaches for its construction: the first (trend approach) is based on information whether the cycle is above or below the long-term trend, and whether it is increasing or decreasing; the second (growth rate approach) is whether the growth rates are above zero, and they are growing or decreasing compared to the neighboring time period; the third (fact-expectation approach) is whether estimates of the current situation and expectations are above or below zero (trend, long–term average, etc.). The work used data on the dynamics of output, the volume of future orders and the results of surveys of the manufacturing industry. The article shows that the first approach works best and allows you to clearly define the phases and turning points of the business cycle. The second approach makes it possible to identify phases of the business cycle, but has some disadvantages: jumps in the series from one quadrant to another and back near the boundary values occur, which complicates the analysis. The third approach is not acceptable for constructing a tracer, since it does not allow us to fully identify all phases of the business cycle and may have dynamics that do not correspond to the general logic of business cycles. The article also demonstrates the high relationship between the business cycles of the manufacturing industry and the business climate indicator of the Bank of Russia (data from business surveys of enterprises), indicating a change in the dynamics of the business cycle with 1-3 months ahead of statistics. Given the faster publication of survey results than statistical data, it can be used as a leading indicator.

Ecological dynamics in the third space: a diffractive analysis of academic development

In this article, we conceptualise the maintenance and evolution of third space practice using an ecological heuristic. This considers the dynamic balance between stabilising and destabilising processes that require third space practitioners (particularly academic developers) to be active curators of this space. These processes drive the phases of the adaptive cycle as it evolves from an epistemologically singular perspective towards one that accommodates epistemological plurality. A pictorial representation of the ecological dynamics is offered as a frame to support the construction of a personal professional narrative. This provides an exemplar of reflection on practice, and highlights the need for epistemic humility within this professional arena.

ExoBand, A Passive Wearable Device as a Walking Aid in Neuromuscular Patients: First Quantitative Assessment.

Exoband (by Moveo, Padova, Italy) functions as a walking brace, comprising a belt and two leg loops connected by a mechanism that stores energy during the initial phase of the gait cycle and releases it in the subsequent phase. This enhances hip flexor thrust, leading to functional improvement in walking for individuals with conditions characterized by proximal weakness. It has been approved as a passive wearable device for individuals with impaired walking abilities. Objective of this study was to establish a protocol to assess the use of Exoband in patients with various neuromuscular disorders. This exploratory retrospective study includes consecutive patients diagnosed with neuromuscular disorders (CIDP, motor polyneuropathy, MND), exhibiting a proximal involvement and gait abnormalities. The evaluation protocol incorporated specific walking-related outcome measures, the 10-meter walk test (10mWT), Time-up-and-go test (TUG), and 2-minute walking test (2MWT). The assessments were conducted both with and without the Exoband under standard conditions. Eight patients (6 males, aged 60-78 years) were tested. An increase in velocity was observed in the 10mWT (median 13.4 sec, IQR 12.0-15.7 vs. 12.2 sec, IQR 11.3-14.2 seconds, p < 0.05) and the TUG (14.0 sec, IQR 13-16.2 vs 13.35 sec, IQR 11-13.8; p < 0.05, by non-parametric Wilcoxon test), and a trend of increase in 2MWT (median 88.2 vs 92.6 m, n.s.). Six out of 8 patients reported subjective benefits from the very first use, including improved walking stability, speed, confidence, and reduced fatigue. Our protocol provides a quantitative assessment of Exoband usefulness for patients affected by neuropathies with gait abnormalities. Further investigations are warranted to assess the long-term effects of its regular Exoband use, its efficacy in specific neuromuscular diseases, and its potential role as a rehabilitation device.

Attractive Caregiving: Women’s Preference for Men that Care for Children and the Role of Nurturance Motivation and Menstrual Cycle Phase

Attractive Caregiving: Women’s Preference for Men that Care for Children and the Role of Nurturance Motivation and Menstrual Cycle Phase

Activation of Peroxisome Proliferator-Activated Receptor-β/δ (PPARβ/δ) in Keratinocytes by Endogenous Fatty Acids

Nuclear hormone receptors exist in dynamic equilibrium between transcriptionally active and inactive complexes dependent on interactions with ligands, proteins, and chromatin. The present studies examined the hypothesis that endogenous ligands activate peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in keratinocytes. The phorbol ester treatment or HRAS infection of primary keratinocytes increased fatty acids that were associated with enhanced PPARβ/δ activity. Fatty acids caused PPARβ/δ-dependent increases in chromatin occupancy and the expression of angiopoietin-like protein 4 (Angptl4) mRNA. Analyses demonstrated that stearoyl Co-A desaturase 1 (Scd1) mediates an increase in intracellular monounsaturated fatty acids in keratinocytes that act as PPARβ/δ ligands. The activation of PPARβ/δ with palmitoleic or oleic acid causes arrest at the G2/M phase of the cell cycle of HRAS-expressing keratinocytes that is not found in similarly treated HRAS-expressing Pparb/d-null keratinocytes. HRAS-expressing Scd1-null mouse keratinocytes exhibit enhanced cell proliferation, an effect that is mitigated by treatment with palmitoleic or oleic acid. Consistent with these findings, the ligand activation of PPARβ/δ with GW0742 or oleic acid prevented UVB-induced non-melanoma skin carcinogenesis, an effect that required PPARβ/δ. The results from these studies demonstrate that PPARβ/δ has endogenous roles in keratinocytes and can be activated by lipids found in diet and cellular components.

Incorporating pathological gait into patient-specific finite element models of the haemophilic ankle.

Haemarthrosis is an inherent clinical feature of haemophilia, a disease characterised by an absence or reduction in clotting proteins. Patients with severe haemophilia experience joint bleeding leading to blood-induced ankle arthropathy (haemarthropathy). Altered biomechanics of the ankle have been reported in people with haemophilia; however, the consequence of this on joint health is little understood. The aim of this study was to assess the changes in joint contact due to haemophilia disease-specific gait features using patient-specific modelling, to better understand the link between biomechanics and joint outcomes. Four, image-based, finite element models of haemophilic ankles were simulated through consecutive events in the stance phase of gait, using both patient-specific and healthy control group (n = 36) biomechanical inputs. One healthy control FE model was simulated through the healthy control stance phase of the gait cycle for a point of comparison. The method developed allowed cartilage contact mechanics to be assessed throughout the loading phase of the gait cycle. This showed areas of increased contact pressure in the medial and lateral regions of the talar dome, which may be linked to collapse in these regions. This method may allow the relationship between structure and function in the tibiotalar joint to be better understood.

Chemosensitizing effect of pentoxifylline in sensitive and multidrug-resistant non-small cell lung cancer cells

Aim: Multidrug resistance (MDR) is frequent in non-small cell lung cancer (NSCLC) patients, which can be due to its fibrotic stroma. This work explores the combination of pentoxifylline, an anti-fibrotic and chitinase 3-like-1 (CHI3L1) inhibitor drug, with conventional chemotherapy to improve NSCLC treatment. Methods: The effect of pentoxifylline in the expression levels of P-glycoprotein (P-gp), CHI3L1 and its main downstream proteins, as well as on cell death, cell cycle profile, and P-gp activity was studied in two pairs of sensitive and MDR counterpart NSCLC cell lines (NCI-H460/NCI-H460/R and A549/A549-CDR2). Association studies between CHI3L1 gene expression and NSCLC patients’ survival were performed using The Cancer Genome Atlas (TCGA) analysis. The sensitizing effect of pentoxifylline to different drug regimens was evaluated in both sensitive and MDR NSCLC cell lines. The cytotoxicity of the drug combinations was assessed in MCF10A non-tumorigenic cells. Results: Pentoxifylline slightly decreased the expression levels of CHI3L1, β-catenin and signal transducer and activator of transcription 3 (STAT3), and caused a significant increase in the G1 phase of the cell cycle in both pairs of NSCLC cell lines. A significant increase in the % of cell death was observed in the sensitive NCI-H460 cell line. TCGA analysis revealed that high levels of CHI3L1 are associated with low overall survival (OS) in NSCLC patients treated with vinorelbine. Moreover, pentoxifylline sensitized both pairs of sensitive and MDR NSCLC cell lines to the different drug regimens, without causing significant toxicity to non-tumorigenic cells. Conclusion: This study suggests the possibility of combining pentoxifylline with chemotherapy to increase NSCLC therapeutic response, even in cases of MDR.

A mechanistic insight into the anticancer potentials of resveratrol: Current perspectives.

Resveratrol is a widely recognized polyphenolic phytochemical found in various plants and their fruits, such as peanuts, grapes, and berry fruits. It is renowned for its several health advantages. The phytochemical is well known for its anticancer properties, and a substantial amount of clinical evidence has also established its promise as a chemotherapeutic agent. This study focuses on assessing the anticancer properties of resveratrol and gaining insight into the underlying molecular mechanisms. It also evaluates the biopharmaceutical, toxicological characteristics, and clinical utilization of resveratrol to determine its suitability for further development as a reliable anticancer agent. Therefore, the information about preclinical and clinical studies was collected from different electronic databases up-to-date (2018-2023). Findings from this study revealed that resveratrol has potent therapeutic benefits against various cancers involving different molecular mechanisms, such as induction of oxidative stress, cytotoxicity, inhibition of cell migration and invasion, autophagy, arresting of the S phase of the cell cycle, apoptotic, anti-angiogenic, and antiproliferative effects by regulating different molecular pathways including PI3K/AKT, p38/MAPK/ERK, NGFR-AMPK-mTOR, and so on. However, the compound has poor oral bioavailability due to reduced absorption; this limitation is overcome by applying nanotechnology (nanoformulation of resveratrol). Clinical application also showed therapeutic benefits in several types of cancer with no serious adverse effects. We suggest additional extensive studies to further check the efficacy, safety, and long-term hazards. This could involve a larger number of clinical samples to establish the compound as a reliable drug in the treatment of cancer.

Metformin as an Enhancer for the Treatment of Chemoresistant CD34+ Acute Myeloid Leukemia Cells.

Acute myeloid leukemia is the second most frequent type of leukemia in adults. Due to a high risk of development of chemoresistance to first-line chemotherapy, the survival rate of patients in a 5-year period is below 30%. One of the reasons is that the AML population is heterogeneous, with cell populations partly composed of very primitive CD34+CD38- hematopoietic stem/progenitor cells, which are often resistant to chemotherapy. First-line treatment with cytarabine and idarubicin fails to inhibit the proliferation of CD34+CD38- cells. In this study, we investigated Metformin's effect with or without first-line conventional chemotherapy, or with other drugs like venetoclax and S63845, on primitive and undifferentiated CD34+ AML cells in order to explore the potential of Metformin or S63845 to serve as adjuvant therapy for AML. We found that first-line conventional chemotherapy treatment inhibited the growth of cells and arrested the cells in the S phase of the cell cycle; however, metformin affected the accumulation of cells in the G2/M phase. We observed that CD34+ KG1a cells respond better to lower doses of cytarabine or idarubicin in combination with metformin. Also, we determined that treatment with cytarabine, venetoclax, and S63845 downregulated the strong tendency of CD34+ KG1a cells to form cell aggregates in culture due to the downregulation of leukemic stem cell markers like CD34 and CD44, as well as adhesion markers. Also, we found that idarubicin slightly upregulated myeloid differentiation markers, CD11b and CD14. Treatment with cytarabine, idarubicin, venetoclax, metformin, and S63845 upregulated some cell surface markers like HLA-DR expression, and metformin upregulated CD9, CD31, and CD105 cell surface marker expression. In conclusion, we believe that metformin has the potential to be used as an adjuvant in the treatment of resistant-to-first-line-chemotherapy AML cells. Also, we believe that the results of our study will stimulate further research and the potential use of changes in the expression of cell surface markers in the development of new therapeutic strategies.