-
Frontiers in Endocrinology 2023The most common cause of infertility and metabolic problems among women of reproductive age is polycystic ovary syndrome (PCOS), a multifaceted disorder. It is an... (Review)
Review
The most common cause of infertility and metabolic problems among women of reproductive age is polycystic ovary syndrome (PCOS), a multifaceted disorder. It is an endocrine disorder that occurs in approximately one in seven women. Among these PCOS patients, two thirds will not ovulate on a regular basis and seek treatment for ovulation induction. The symptoms vary in their severity, namely ovulation disorders, excessive androgen levels, or polycystic ovarian morphology. All these symptoms require a therapeutic approach. Many drugs are used to eradicate PCOS symptoms, like metformin, clomiphene citrate, spironolactone, and pioglitazone. Long-term treatment is required to achieve the desired outcome, which is often accompanied by significant adverse reactions. Some herbs and phytochemicals are equally effective for treating PCOS and produce minimal side effects. Recently, herbal products are gaining popularity due to their wide biological activities, safety, availability, and efficacy. The present review covers aetiology, current treatment, pathophysiology, and detailed pre-clinical and clinical studies on plants and phytochemicals that are proven to be useful for the treatment of symptoms associated with PCOS.
Topics: Polycystic Ovary Syndrome; Humans; Female; Phytotherapy; Phytochemicals; Animals; Plant Extracts
PubMed: 38725974
DOI: 10.3389/fendo.2023.1294406 -
Advanced Healthcare Materials Oct 2023First-aid for severe traumatic injuries in the battlefield or pre-hospital environment, especially for skin defects or visceral rupture, remains a substantial medical...
First-aid for severe traumatic injuries in the battlefield or pre-hospital environment, especially for skin defects or visceral rupture, remains a substantial medical challenge even in the context of the rapidly evolving modern medical technology. Hydrogel-based biomaterials are highly anticipated for excellent biocompatibility and bio-functional designability. Yet, inadequate mechanical and bio-adhesion properties limit their clinical application. To address these challenges, a kind of multifunctional hydrogel wound dressing is developed with the collective multi-crosslinking advantages of dynamic covalent bonds, metal-catechol chelation, and hydrogen bonds. The mussel-inspired design and zinc oxide-enhanced cohesion strategy collaboratively reinforce the hydrogel's bio-adhesion in bloody or humoral environments. The pH-sensitive coordinate Zn -catechol bond and dynamic Schiff base with reversible breakage and reformation equip the hydrogel dressing with excellent self-healing and on-demand removal properties. In vivo evaluation in a rat ventricular perforation model and Methicillin-resistant Staphylococcus aureus (MRSA)-infected full-thickness skin defect model reveal excellent hemostatic, antibacterial and pro-healing effectiveness of the hydrogel dressing, demonstrating its great potential in dealing with severe bleeding and infected full-thickness skin wounds.
Topics: Animals; Rats; Hemostatics; Hydrogels; Methicillin-Resistant Staphylococcus aureus; Anti-Bacterial Agents; Bandages; Catechols
PubMed: 37335228
DOI: 10.1002/adhm.202300312 -
Journal of Controlled Release :... Sep 2023Microneedle Array Patches (MAPs) are an emerging dosage form that creates transient micron-sized disruptions in the outermost physical skin barrier, the stratum corneum,...
Microneedle Array Patches (MAPs) are an emerging dosage form that creates transient micron-sized disruptions in the outermost physical skin barrier, the stratum corneum, to facilitate delivery of active pharmaceutical ingredients to the underlying tissue. Numerous MAP products are proposed and there is significant clinical potential in priority areas such as vaccination. However, since their inception scientists have hypothesized about the risk of a clinically significant MAP-induced infection. Safety data from two major Phase 3 clinical trials involving hundreds of participants, who in total received tens of thousands of MAP applications, does not identify any clinically significant infections. However, the incumbent data set is not extensive enough to make definitive generalizable conclusions. A comprehensive assessment of the infection risk is therefore advised for MAP products, and this should be informed by clinical and pre-clinical data, theoretical analysis and informed opinions. In this article, a group of key stakeholders identify some of the key product- and patient-specific factors that may contribute to the risk of infection from a MAP product and provide expert opinions in the context of guidance from regulatory authorities. Considerations that are particularly pertinent to the MAP dosage form include the specifications of the finished product (e.g. microbial specification), it's design features, the setting for administration, the skill of the administrator, the anatomical application site, the target population and the clinical context. These factors, and others discussed in this article, provide a platform for the development of MAP risk assessments and a stimulus for early and open dialogue between developers, regulatory authorities and other key stakeholders, to expedite and promote development of safe and effective MAP products.
Topics: Humans; Administration, Cutaneous; Drug Delivery Systems; Epidermis; Needles; Pharmaceutical Preparations; Risk Assessment; Skin; Clinical Trials, Phase III as Topic
PubMed: 37437849
DOI: 10.1016/j.jconrel.2023.07.001 -
Journal of Clinical Apheresis Oct 2023Therapeutic plasma exchange (TPE) is commonly performed using membrane-based TPE (mTPE) and is prone to filter failure.
BACKGROUND AND OBJECTIVES
Therapeutic plasma exchange (TPE) is commonly performed using membrane-based TPE (mTPE) and is prone to filter failure.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We report on 46 patients, with a total of 321 mTPE treatments using the NxStage machine. This was a retrospective study with an aim to evaluate the effect of heparin, pre-filter saline dilution and the impact of total plasma volume exchanged (< 3 L vs. ≥3 L) on the rate of filter failure. Primary outcome was the overall rate of filter failure. Secondary outcomes included factors that may have indirectly influenced the rate of filter failure, including hematocrit, platelet count, replacement fluid (Fresh Frozen Plasma vs. albumin), and access type.
RESULTS
We found that treatments that received both pre-filter heparin and saline had a statistically significant decrease in filter failure rate as compared to those that received neither (28.6% vs. 5.3%, P = .001), and compared to the treatments that received pre-filter heparin alone (14.2% vs. 5.3%, P = .015). In treatments that received both pre-filter heparin and saline predilution, we noted a significantly higher filter failure rate when the plasma volume exchanged was ≥3 L as compared to those that had <3 L exchanged (12.2% vs. 0.9%, P = .001).
CONCLUSIONS
Rate of filter failure in mTPE can be reduced by implementing several therapeutic interventions including pre-filter heparin and pre-filter saline solution. These interventions were not associated with any clinically significant adverse events. Despite the above-mentioned interventions, large plasma volume exchanges of ≥3 L can negatively impact filter life.
Topics: Humans; Plasma Exchange; Retrospective Studies; Plasmapheresis; Heparin; Hemofiltration; Saline Solution
PubMed: 37287385
DOI: 10.1002/jca.22065 -
Food Research International (Ottawa,... Oct 2023Roasting could modify the protein structure/conformation, contributing to changes in functional properties. Here we investigated the effects of pre-roasting on the...
Roasting could modify the protein structure/conformation, contributing to changes in functional properties. Here we investigated the effects of pre-roasting on the extraction efficiency, structural and functional properties of pea protein concentrates and isolates (PPC and PPI) produced from yellow split peas. The shorter roasting times (150 °C, 10 and 20 min) had little effect on protein yields and could increase the solubility of PPC or PPI by ∼ 12% at pH 7 and enhance the solubility of PPI by ∼ 12% (10-min roasting) and ∼ 24% (20-min roasting) at pH 3. However, a longer duration of pre-roasting (150 °C, 30 min) significantly reduced the extraction efficiency of PPC and PPI by ∼ 30% and ∼ 61%, respectively. Meanwhile, pre-roasting had minor effects on SDS-PAGE profiles and the secondary structures of pea proteins but significantly altered tertiary structures by reducing free sulfhydryl groups, increasing disulfide bonds and surface hydrophobicity. As for the emulsifying properties, pre-roasting improved the emulsion ability index (EAI) of PPC and PPI but decreased the emulsion stability index (ESI) of PPC and had no significant effect on PPI. Moreover, PPC and PPI with shorter pre-roasting duration (10 and 20 min) had endothermic peaks and showed a slight decrease in the denaturation temperature (T) and the onset temperature (T), respectively. Overall, the study demonstrated that controlled pre-roasting at 150 °C for 10 min and 20 min altered protein structures (mainly tertiary structures), improving the solubility and EAI of pea proteins at pH 7, while retaining their thermal properties in comparison to unroasted samples.
Topics: Emulsions; Pea Proteins; Protein Conformation; Electrophoresis, Polyacrylamide Gel; Lathyrus
PubMed: 37689931
DOI: 10.1016/j.foodres.2023.113180 -
Journal of Artificial Organs : the... Dec 2023Online hemodiafiltration (OHDF) for renal replacement therapy has two modes: pre- (pre-OHDF) and post-dilution OHDF (post-OHDF). To elucidate the precise differences...
Online hemodiafiltration (OHDF) for renal replacement therapy has two modes: pre- (pre-OHDF) and post-dilution OHDF (post-OHDF). To elucidate the precise differences between the two modes, a clinical study was performed using the same polysulfone hemodiafilters in the same patients. Eight patients were treated with ABH-22PA for 6 weeks: 3 weeks of pre-OHDF (with substitution volumes of 24, 36, and 48 L) and 3 weeks of post-OHDF (6, 8, and 10 L). The reduction ratios of urea, uric acid (UA), creatinine (CRE), inorganic phosphorus (iP), beta-2-microglobulin (β-MG), and alpha-1-microglobulin (α-MG) were evaluated. The removal amounts of β-MG, α-MG, and albumin were also evaluated by analyzing the spent dialysis fluids. The types and numbers of adverse events (AEs) and device malfunctions were recorded. The reduction ratios of urea, UA, CRE, iP, and β-MG were comparable among all conditions, while that of α-MG tended to be slightly higher in post-OHDF than in pre-OHDF. The removal amounts of α-MG and albumin in pre-OHDF and post-OHDF were significantly greater with the maximum substitution volume than with the minimum volume. However, the selective removal indices, which were obtained by dividing the amount of α-MG removed by the albumin level, tended to be slightly higher in pre- than in post-OHDF. No device-related AEs or device malfunctions occurred in either mode. No significant differences in inflammatory responses, evaluated by high-sensitivity C-reactive protein and interleukin-6, were observed. This study provides removal performance and safety data regarding the application of ABH-22PA for pre- and post-OHDF.
Topics: Humans; Hemodiafiltration; Renal Dialysis; Dialysis Solutions; Albumins; Urea; beta 2-Microglobulin; Creatinine
PubMed: 36513897
DOI: 10.1007/s10047-022-01379-4 -
Journal of Ethnopharmacology Dec 2023Sophora davidii (Franch.) Skeels Flower (SDF) is a characteristic folk medicine in Yunnan and Guizhou, which can be used to prevent the occurrence of tumors. The extract...
ETHNOPHARMACOLOGICAL RELEVANCE
Sophora davidii (Franch.) Skeels Flower (SDF) is a characteristic folk medicine in Yunnan and Guizhou, which can be used to prevent the occurrence of tumors. The extract of SDF (SDFE) is confirmed to be antitumor by pre-experiment. However, effective components and anticancer mechanisms of SDFE are still unclear.
AIM OF THE STUDY
The purpose of this study was to explore the material basis and action mechanisms of SDFE in the treatment of non-small cell carcinoma (NSCLC).
MATERIALS AND METHODS
UHPLC-Q-Exactive-Orbitrap-MS/MS was used to identify the chemical components of SDFE. The network pharmacology was applied to screen out the main active components, core genes and related signaling pathways of SDFE in treatment of NSCLC. Molecular docking was used to predict the affinity of major components and core targets. The database was applied to predict the mRNA and protein expression levels of core targets in NSCLC. Finally, the experiments in vitro were performed by CCK-8, flow cytometry and western blot (WB).
RESULTS
In this study, 98 chemical components were identified by UHPLC-Q-Exactive- Orbitrap-MS/MS. 5 main active components (namely quercetin, genistein, luteolin, kaempferol, isorhamnetin), 10 core genes (namely TP53, AKT1, STAT3, SRC, MAPK3, EGFR, JUN, EP300, TNF, PIK3R1) and 20 pathways were screened out through network pharmacology. The 5 active ingredients were molecularly docked with the core genes, and most the LibDockScore values were higher than 100. The data collected from the database indicated that TP53, AKT1 and PIK3R1 were closely related to the occurrence of NSCLC. The results of experiment in vitro showed that SDFE promoted NSCLC cells apoptosis by down-regulating the phosphorylation of PI3K, AKT and MDM2, up-regulating the phosphorylation of P53, inhibiting the expression of Bcl-2 and up-regulating the expression of Bax.
CONCLUSION
The combination of network pharmacology, molecular docking, database validation, and in vitro experimental validation effectively demonstrates that SDFE can promote cell apoptosis by regulating PI3K-AKT/MDM2-P53 signaling pathway, so as to treat NSCLC.
Topics: Carcinoma, Non-Small-Cell Lung; Sophora; Molecular Docking Simulation; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Tandem Mass Spectrometry; Tumor Suppressor Protein p53; Lung Neoplasms; China; Carcinoma; Transcription Factors; Plant Extracts; Drugs, Chinese Herbal
PubMed: 37400006
DOI: 10.1016/j.jep.2023.116815 -
Journal of Artificial Organs : the... Mar 2024Online hemodiafiltration (OL-HDF) is a treatment modality using diffusion and ultrafiltration. There are two types of dilution methods in OL-HDF: pre-dilution, which is...
Online hemodiafiltration (OL-HDF) is a treatment modality using diffusion and ultrafiltration. There are two types of dilution methods in OL-HDF: pre-dilution, which is commonly provided in Japan, and post-dilution, which is commonly provided in Europe. The optimal OL-HDF method for individual patients is not well studied. In this study, we compared the clinical symptoms, laboratory data, spent dialysate, and adverse events of pre- and post-dilution OL-HDF. We conducted a prospective study of 20 patients who underwent OL-HDF between January 1, 2019 and October 30, 2019. Their clinical symptoms and dialysis efficacy were evaluated. All patients underwent OL-HDF every 3 months in the following sequence: first pre-dilution, post-dilution, and second pre-dilution. We evaluated 18 patients for the clinical study and 6 for the spent dialysate study. No significant differences in spent dialysates regarding small and large solutes, blood pressure, recovery time, and clinical symptoms were observed between the pre- and post-dilution methods. However, the serum α1-microglobulin level in post-dilution OL-HDF was lower than that in pre-dilution OL-HDF (first pre-dilution: 124.8 ± 14.3 mg/L; post-dilution: 116.6 ± 13.9 mg/L; second pre-dilution: 125.8 ± 13.0 mg/L; first pre-dilution vs. post-dilution, post-dilution vs. second pre-dilution, and first pre-dilution vs. second pre-dilution: p = 0.001, p < 0.001, and p = 1.000, respectively). The most common adverse event was an increase in transmembrane pressure in the post-dilution period. Compared to pre-dilution, the post-dilution method decreased the α1-microglobulin level; however, there were no significant differences in clinical symptoms or laboratory data.
Topics: Humans; Hemodiafiltration; Prospective Studies; Renal Dialysis; Blood Pressure; Dialysis Solutions
PubMed: 37010653
DOI: 10.1007/s10047-023-01391-2 -
Therapeutic Delivery Dec 2023Naringenin belongs to the flavanones and is mainly found in fruits (grapefruit and oranges) and vegetables. Naringenin exhibits lipid-lowering and insulin-like... (Review)
Review
Naringenin belongs to the flavanones and is mainly found in fruits (grapefruit and oranges) and vegetables. Naringenin exhibits lipid-lowering and insulin-like characteristics and is used to treat osteoporosis, cancer and cardiovascular disorders. Their incorporation into drug formulations offers several advantages, including enhanced solubility, improved bioavailability and targeted delivery. Naringin-based formulations are beneficial in cancer, for example controlling breast and prostate cancer by inhibition of CYP19. Naringin suppresses the PI3K/AKT signalling pathway, it triggers autophagy, which effectively halts the proliferation of gastric cancer cells. Naringin and naringenin co-administration or pre-administration has enhanced the target drug's potency and produced a synergistic effect. This published study demonstrates the potential applications of Naringin and Naringenin as recognized bio-enhancers.
Topics: Male; Humans; Bioenhancers; Phosphatidylinositol 3-Kinases; Flavanones; Neoplasms
PubMed: 38088094
DOI: 10.4155/tde-2023-0086 -
Current Protocols Aug 2023Angiogenic sprouting, the formation of new blood vessels from pre-existing vasculature, is tightly regulated by the properties of the surrounding tissue...
Angiogenic sprouting, the formation of new blood vessels from pre-existing vasculature, is tightly regulated by the properties of the surrounding tissue microenvironment. Although the extracellular matrix has been shown to be a major regulator of this process, it is not clear how individual biochemical and mechanical properties influence endothelial cell sprouting. This information gap is largely due to the lack of suitable in vitro models that recapitulate angiogenic sprouting in a 3D environment with independent control over matrix properties. Here, we present protocols for the preparation of endothelial cell spheroid-laden synthetic, dextran-based hydrogels, which serve as a highly tunable 3D scaffold. The adjustment of the hydrogels' adhesiveness, stiffness, and degradability is demonstrated in detail. Finally, we describe assays to elucidate how individual matrix properties regulate angiogenic sprouting, including their analysis by immunofluorescence staining and imaging. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Synthesis of methacrylated dextran (DexMA) Basic Protocol 2: Generation of endothelial cell spheroids in microwells Basic Protocol 3: Endothelial cell sprouting in hydrogels of tunable stiffness Basic Protocol 4: Endothelial cell sprouting in hydrogels of tunable adhesiveness Basic Protocol 5: Endothelial cell sprouting in hydrogels of tunable degradability Basic Protocol 6: Imaging of endothelial cell spheroid-laden hydrogels Support Protocol 1: Preparation of pro-angiogenic cocktail for endothelial cell sprouting.
Topics: Hydrogels; Extracellular Matrix; Endothelial Cells; Cardiovascular Physiological Phenomena; Neovascularization, Physiologic
PubMed: 37555756
DOI: 10.1002/cpz1.859