Ulvophyte Green Algae Caulerpa lentillifera: Metabolites Profile and Antioxidant, Anticancer, Anti-Obesity, and In Vitro Cytotoxicity Properties.

Marine algae have excellent bioresource properties with potential nutritional and bioactive therapeutic benefits, but studies regarding Caulerpa lentillifera are limited. This study aims to explore the metabolites profile and the antioxidant, anticancer, anti-obesity, and in vitro cytotoxicity properties of fractionated ethanolic extract of C. lentillifera using two maceration and soxhlet extraction methods. Dried simplicia of C. lentillifera was mashed and extracted in ethanol solvent, concentrated and evaporated, then sequentially partitioned with equal volumes of ethyl acetate and n-Hexane. Six samples were used in this study, consisting of ME (Maceration-Ethanol), MEA (Maceration-Ethyl Acetate), MH (Maceration-n-Hexane), SE (Soxhletation-Ethanol), SEA (Soxhletation-Ethyl Acetate), and SH (Soxhletation-n-Hexane). Non-targeted metabolomic profiling was determined using LC-HRMS, while antioxidant, anti-obesity, and anticancer cytotoxicity were determined using DPPH and ABTS, lipase inhibition, and MTT assay, respectively. This study demonstrates that C. lentillifera has several functional metabolites, antioxidant capacity (EC50 MH is very close to EC50 of Trolox), as well as anti-obesity properties (EC50 MH < EC50 orlistat, an inhibitor of lipid hydrolyzing enzymes), which are useful as precursors for new therapeutic approaches in improving obesity-related diseases. More interestingly, ME, MH, and SE are novel bioresource agents for anticancer drugs, especially for hepatoma, breast, colorectal, and leukemia cancers. Finally, C. lentillifera can be a nutraceutical with great therapeutic benefits.

Autophagy and Female Fertility: Mechanisms, Clinical Implications, and Emerging Therapies.

Autophagy, an evolutionarily conserved cellular mechanism essential for maintaining internal stability, plays a crucial function in female reproductive ability. In this review, we discuss the complex interplay between autophagy and several facets of female reproductive health, encompassing pregnancy, ovarian functions, gynecologic malignancies, endometriosis, and infertility. Existing research emphasizes the crucial significance of autophagy in embryo implantation, specifically in the endometrium, highlighting its necessity in ensuring proper fetal development. Although some knowledge has been gained, there is still a lack of research on the specific molecular impacts of autophagy on the quality of oocytes, the growth of follicles, and general reproductive health. Autophagy plays a role in the maturation, quality, and development of oocytes. It is also involved in reproductive aging, contributing to reductions in reproductive function that occur with age. This review explores the physiological functions of autophagy in the female reproductive system, its participation in reproductive toxicity, and its important connections with the endometrium and embryo. In addition, this study investigates the possibility of emerging treatment approaches that aim to modify autophagy, using both natural substances and synthetic molecules, to improve female fertility and reproductive outcomes. Additionally, this review intends to inspire future exploration into the intricate role of autophagy in female reproductive health by reviewing recent studies and pinpointing areas where current knowledge is lacking. Subsequent investigations should prioritize the conversion of these discoveries into practical uses in the medical field, which could potentially result in groundbreaking therapies for infertility and other difficulties related to reproduction. Therefore, gaining a comprehensive understanding of the many effects of autophagy on female fertility would not only further the field of reproductive biology but also open new possibilities for diagnostic and treatment methods.

Anatomical structures in the maxillary sinus related to lateral sinus elevation: a cone beam computed tomographic analysis.

OBJECTIVES: The objective of this study is to evaluate the anatomical structures in the maxillary sinus with relation to lateral approach sinus elevation utilizing cone beam computed tomography (CT) scans taken prior to sinus elevation surgery. MATERIALS AND METHODS: A total of 150 CT images were acquired from 150 patients (90 men and 60 women; mean age, 49.4 years, range 23-86 years) who were being treated with implant-supported restorations in the posterior edentulous maxilla. Of the 150 CT scans, 65 were of the right sinus and 85 of the left sinus. Measurements of the anatomical structures in the maxillary sinus were conducted on the CT images. RESULTS: In the mean width of the lateral wall, there were statistically significant values among the measurement points (P < 0.05). The anterior area of the sinus lateral wall was thicker than the posterior lateral wall. There was a statistically significant difference between the vessel diameter and lateral wall width (P < 0.05). As sinus lateral wall width increased, so did the vessel diameter. The mean distance to the inferior border of the vessel from the sinus floor and from the alveolar crest was 8.25 and 17.03 mm, respectively. The intraosseous group among the vessel position was 64.3%, so the intraosseous vessel could be visualized in CT scans at 64.3%. In angle A, the group of less than 30° was 4.8%. Schneiderian membrane perforation by narrow angle had a low risk. The prevalence of the septa related to Schneiderian membrane perforation was 44%. The distance to the inferior border of the vessel from the alveolar crest being less than 15 mm was 31%. The vessel diameter greater than 1 mm was 37.8%. CONCLUSIONS: Based on present research about utilizing cone beam CT scans for sinus elevation, the alteration of the lateral approach sinus elevation technique is highly recommended if complications such as membrane perforation or bleeding are expected.

Development of Clinically Optimized Sitagliptin and Dapagliflozin Complex Tablets: Pre-Formulation, Formulation, and Human Bioequivalence Studies.

The purpose of this study is to derive an optimal drug release formulation with human clinical bioequivalence in developing a sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate fixed-dose combination (FDC) tablet as a treatment for type 2 diabetes mellitus. As a treatment for type 2 diabetes mellitus, the combined prescription of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors is common. Therefore, this study simplified the number of individual drugs taken and improved drug compliance by developing FDC tablets containing sitagliptin phosphate monohydrate as a DPP-4 inhibitor and dapagliflozin propanediol hydrate as an SGLT-2 inhibitor. To derive the optimal dosage form, we prepared single-layer tablets, double-layer tablets, and dry-coated tablets and evaluated the drug control release ability, tableting manufacturability, quality, and stability. Single-layer tablets caused problems with stability and drug dissolution patterns. When the dissolution test was performed on the dry-coated tablets, a corning effect occurred, and the core tablet did not completely disintegrate. However, in the quality evaluation of the double-layer tablets, the hardness was 12-14 kilopond, the friability was 0.2%, and the disintegration was within 3 min. In addition, the stability test revealed that the double-layer tablet was stable for 9 months under room temperature storage conditions and 6 months under accelerated storage conditions. In the drug release test, only the FDC double-layer tablet showed the optimal drug release pattern that satisfied each drug release rate. In addition, the FDC double-layer tablet showed a high dissolution rate of over 80% in the form of immediate-release tablets within 30 min in a pH 6.8 dissolution solution. In the human clinical trial, we co-administered a single dose of a sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate FDC double-layered tablet and the reference drug (Forxiga®, Januvia®) in healthy adult volunteers. This study showed clinically equivalent results in the stability and pharmacodynamic characteristics between the two groups.

Natural Products as New Approaches for Treating Bladder Cancer: From Traditional Medicine to Novel Drug Discovery.

Bladder cancer (BC) is a heterogeneous disease that a tumor develops in the bladder lining and in some cases, the bladder muscle. Chemotherapy and immunotherapy are commonly used to treat bladder cancer. However, chemotherapy can cause burning and irritation in the bladder while BCG immunotherapy, which is the main type of intravesical immunotherapy for bladder cancer, can also cause burning in the bladder and flu-like symptoms. Thus, drugs originating from natural products have attracted much attention due to the reports that they have anti-cancer properties with low adverse effects. In this study, eighty-seven papers that dealt with natural products preventing or treating bladder cancer were reviewed. The studies were classified into the following mechanism: 71 papers on cell death, 5 papers on anti-metastasis, 3 papers on anti-angiogenesis, 1 paper on anti-resistance, and 7 papers on clinical trials. Most of the natural products that induced apoptosis up-regulated proteins such as caspase-3 and caspase-9. Regarding anti-metastasis, MMP-2 and MMP-9 are regulated frequently. Regarding anti-angiogenesis, HIF-1α and VEGF-A are down-regulated frequently. Nevertheless, the number of papers regarding anti-resistance and clinical trial are too few, so more studies are needed. In conclusion, this database will be useful for future in vivo studies of the anti-bladder cancer effect of natural products, in the process of selecting materials used for the experiment.

Unraveling the therapeutic potential of natural products in the prevention and treatment of leukemia.

Leukemia is a heterogeneous group of hematological malignancies distinguished by differentiation blockage and uncontrolled proliferation of myeloid or lymphoid progenitor cells in the bone marrow (BM) and peripheral blood (PB). There are various types of leukemia in which intensive chemotherapy regimens or hematopoietic stem cell transplantation (HSCT) are now the most common treatments associated with severe side effects and multi-drug resistance in leukemia cells. Therefore, it is crucial to develop novel therapeutic approaches with adequate therapeutic efficacy and selectively eliminate leukemic cells to improve the consequences of leukemia. Medicinal plants have been utilized for ages to treat multiple disorders due to their diverse bioactive compounds. Plant-derived products have been used as therapeutic medication to prevent and treat many types of cancer. Over the last two decades, 50 % of all anticancer drugs approved worldwide are from natural products and their derivatives. Therefore this study aims to review natural products such as polyphenols, alkaloids, terpenoids, nitrogen-containing, and organosulfur compounds as antileukemic agents. Current investigations have identified natural products efficiently destroy leukemia cells through diverse mechanisms of action by inhibiting proliferation, reactive oxygen species production, inducing cell cycle arrest, and apoptosis in both in vitro, in vivo, and clinical studies. Current investigations have identified natural products as suitable promising chemotherapeutic and chemopreventive agents. It played an essential role in drug development and emerged as a possible source of biologically active metabolites for therapeutic interventions, especially in leukemia. DATA AVAILABILITY: Data will be made available on request.

Dietary Supplementation of Caulerpa racemosa Ameliorates Cardiometabolic Syndrome via Regulation of PRMT-1/DDAH/ADMA Pathway and Gut Microbiome in Mice.

This study evaluated the effects of an aqueous extract of Caulerpa racemosa (AEC) on cardiometabolic syndrome markers, and the modulation of the gut microbiome in mice administered a cholesterol- and fat-enriched diet (CFED). Four groups of mice received different treatments: normal diet, CFED, and CFED added with AEC extract at 65 and 130 mg/kg body weight (BW). The effective concentration (EC50) values of AEC for 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and lipase inhibition were lower than those of the controls in vitro. In the mice model, the administration of high-dose AEC showed improved lipid and blood glucose profiles and a reduction in endothelial dysfunction markers (PRMT-1 and ADMA). Furthermore, a correlation between specific gut microbiomes and biomarkers associated with cardiometabolic diseases was also observed. In vitro studies highlighted the antioxidant properties of AEC, while in vivo data demonstrated that AEC plays a role in the management of cardiometabolic syndrome via regulation of oxidative stress, inflammation, endothelial function (PRMT-1/DDAH/ADMA pathway), and gut microbiota.

Defensive pride and consensus: strength in imaginary numbers.

Failure (Study 1) and attachment separation thoughts (Study 2) caused exaggerated consensus estimates for personal beliefs about unrelated social issues. This compensatory consensus effect was most pronounced among defensively proud individuals, that is, among those with the combination of high explicit and low implicit self-esteem (Study 1) and the combination of high attachment avoidance and low attachment anxiety (Study 2). In Study 3, another form of defensive pride, narcissism, was associated with exaggerated consensual worldview defense after a system-injustice threat. In Study 4, imagined consensus reduced subjective salience of proud individuals' troubling thoughts. Compensatory consensus is seen as a kind of defensive self-affirmation that defensively proud people turn to for insulation from distressing thoughts.

Negative self-synchronization: will I change to be like you when it is bad for me?

The current research examined whether people will attempt to modify internal aspects of the self to make them congruent with others, even when those modifications have negative implications for the self, a phenomenon we refer to as negative self-synchronization. We proposed that negative self-synchronization will occur only for individuals who are securely attached. Across 4 experiments, participants who were high in secure attachment were more likely than those low in attachment security to engage in negative self-synchronization (Experiments 1-4). Attachment style did not moderate positive self-synchronization (Experiments 1 and 2). In addition, priming secure attachment increased negative self-synchronization among insecure participants (Experiments 2 and 3). Conversely, priming insecure attachment decreased negative self-synchronization among secure participants (Experiment 4). Implications of these findings for social synchronization processes, the need to belong, and attachment security are discussed.