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Frontiers in Pharmacology 2024Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug...
Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.
PubMed: 38933670
DOI: 10.3389/fphar.2024.1377924 -
Journal of Cosmetic Dermatology Jun 2024To investigate the relationship between homocysteine (HCY) and androgenetic alopecia (AGA).
OBJECTIVE
To investigate the relationship between homocysteine (HCY) and androgenetic alopecia (AGA).
METHODS
A case control study and two observational experiments on mice were conducted. In the first part, a total of 528 Chinese AGA patients and 500 age-matched healthy controls were included. Serum HCY levels of AGA and controls were compared. In the second part, eight mice were divided into two groups. Both groups of mice had their hair removed. AGA group received a DHT injection, and the other as control group. HCY levels in hair follicles (HFs) were detected by ELISA and compared. In the third part, twelve mice were divided into three groups and fed with different concentrations of methionine. After 4 weeks, serum HCY levels, parameters related to hair growth through observation and HE staining, and expression of immunohistochemistry (IHC) hair-growth-related markers Ki67, VEGF, IGF-1, Krt27, FGF9, and TGF-β1 were compared among the three groups.
RESULTS
In the first part, HCY levels were higher in AGA than the controls of both genders. However, there was no difference in HCY levels between groups with varying severity. Rates of hyperhomocysteinemia was higher in AGA patients than the controls. Logistic regression analysis showed serum HCY levels was positively correlated with the incidence of AGA. In the second part, HCY of the HFs in the AGA group was significantly higher than that in the control group. The third part showed that the increase in serum HCY levels inhibited the growth of mice hair, with the less expressed stimulative markers Ki67, VEGF, IGF-1, Krt27, and FGF9, while there was no difference in the expression of inhibitory markers TGF-β1.
CONCLUSION
There is a potential relationship between HCY and AGA. HCY had an inhibitory effect on hair growth. Further studies are necessary to explore the specific mechanism.
PubMed: 38932477
DOI: 10.1111/jocd.16440 -
Serum lipids may causally affect the occurrence of alopecia areata: A Mendelian randomization study.Skin Research and Technology : Official... Jul 2024The etiology of alopecia areata (AA) in relation to serum lipids remains unclear, thereby prompting our intention to do Mendelian study on this subject.
PURPOSE
The etiology of alopecia areata (AA) in relation to serum lipids remains unclear, thereby prompting our intention to do Mendelian study on this subject.
DESIGN
Two-sample Mendelian randomization (MR) analysis was performed in the study. The inverse variance-weighted method was used as the primary method.
METHODS
In our study, we integrated a set of 123 single-nucleotide polymorphisms (SNPs) into our analysis. These SNPs have been extensively studied and are known to exhibit associations with serum lipids. We sourced these SNPs from a variety of relevant studies and consortia that specifically focus on lipid-related research, such as the MRC Integrative Epidemiology Unit. These carefully curated SNPs were then utilized as instrumental variables in our analysis, allowing us to explore and evaluate the causal relationships between these genetic variants and serum lipids. By incorporating this comprehensive set of SNPs, we aimed to enhance the precision and robustness of our findings, shedding light on the intricate interplay between genetics and serum lipids.
RESULTS
In the MR analysis, a higher total lipid concentration in large low-density lipoprotein (LDL) particles (odds ratio [OR] = 1.502; 95% confidence interval [CI] = 1.086-1.953; p = 0.006), a greater ratio of cholesteryl esters to total lipids in chylomicrons and extremely large very LDL (VLDL) particles (OR = 2.174; 95% CI = 1.300-2.500; p = 0.010), and a greater ratio of cholesterol to total lipids in chylomicrons and extremely large VLDL particles (OR = 2.363;95% CI = 1.556-4.438; p = 0.004), were genetically predicted to be causally associated with an increased risk of AA, while patients with a higher triglyceride to total lipids ratio in chylomicrons and extremely large VLDL particles had a lower risk of AA (OR = 0.481; 95% CI = 0.191-1.270; p = 0.002).
CONCLUSION
This study found that serum lipids may be causally implicated in AA.
Topics: Alopecia Areata; Humans; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Lipids; Genetic Predisposition to Disease
PubMed: 38932455
DOI: 10.1111/srt.13785 -
Pharmaceutics Jun 2024This comprehensive review consolidates insights from two sources to emphasize the transformative impact of scaffold-based drug delivery systems in revolutionizing oral... (Review)
Review
This comprehensive review consolidates insights from two sources to emphasize the transformative impact of scaffold-based drug delivery systems in revolutionizing oral cancer therapy. By focusing on their core abilities to facilitate targeted and localized drug administration, these systems enhance therapeutic outcomes significantly. Scaffolds, notably those coated with anti-cancer agents such as cisplatin and paclitaxel, have proven effective in inhibiting oral cancer cell proliferation, establishing a promising avenue for site-specific drug delivery. The application of synthetic scaffolds, including Poly Ethylene Glycol (PEG) and poly(lactic-co-glycolic acid) (PLGA), and natural materials, like collagen or silk, in 3D systems has been pivotal for controlled release of therapeutic agents, executing diverse anti-cancer strategies. A key advancement in this field is the advent of smart scaffolds designed for sequential cancer therapy, which strive to refine drug delivery systems, minimizing surgical interventions, accentuating the significance of 3D scaffolds in oral cancer management. These systems, encompassing local drug-coated scaffolds and other scaffold-based platforms, hold the potential to transform oral cancer treatment through precise interventions, yielding improved patient outcomes. Local drug delivery via scaffolds can mitigate systemic side effects typically associated with chemotherapy, such as nausea, alopecia, infections, and gastrointestinal issues. Post-drug release, scaffolds foster a conducive environment for non-cancerous cell growth, adhering and proliferation, demonstrating restorative potential. Strategies for controlled and targeted drug delivery in oral cancer therapy span injectable self-assembling peptide hydrogels, nanocarriers, and dual drug-loaded nanofibrous scaffolds. These systems ensure prolonged release, synergistic effects, and tunable targeting, enhancing drug delivery efficiency while reducing systemic exposure. Smart scaffolds, capable of sequential drug release, transitioning to cell-friendly surfaces, and enabling combinatorial therapy, hold the promise to revolutionize treatment by delivering precise interventions and optimized outcomes. In essence, scaffold-based drug delivery systems, through their varied forms and functionalities, are reshaping oral cancer therapy. They target drug delivery efficiency, diminish side effects, and present avenues for personalization. Challenges like fabrication intricacy, biocompatibility, and scalability call for additional research. Nonetheless, the perspective on scaffold-based systems in oral cancer treatment is optimistic, as ongoing advancements aim to surmount current limitations and fully leverage their potential in cancer therapy.
PubMed: 38931923
DOI: 10.3390/pharmaceutics16060802 -
Molecules (Basel, Switzerland) Jun 2024Androgenetic alopecia (AGA) causes thinning hair, but poor hair quality in balding areas and damage from UV radiation have been overlooked. Plant extracts like...
BACKGROUND
Androgenetic alopecia (AGA) causes thinning hair, but poor hair quality in balding areas and damage from UV radiation have been overlooked. Plant extracts like flavonoids (POFs) may improve hair quality in AGA. This study examines POFs' effectiveness in treating AGA-affected hair and repairing UV-induced damage.
METHODS
Hair samples were analyzed using scanning electron microscopy (SEM) to examine surface characteristics, electron paramagnetic resonance (EPR) spectroscopy to measure free radicals in the hair, and spectrophotometry to assess changes in hair properties.
RESULTS
POFs effectively removed hydroxyl radicals from keratinocytes and had antioxidant properties. They also reduced UV-induced damage to AGA hair by mitigating the production of melanin free radicals. Following POF treatment, the reduction in peroxidized lipid loss in AGA hair was notable at 59.72%, thereby effectively delaying the progression of hair color change. Moreover, protein loss decreased by 191.1 μ/g and tryptophan loss by 15.03%, ultimately enhancing hair's tensile strength.
CONCLUSION
compared to healthy hair, hair damaged by AGA shows more pronounced signs of damage when exposed to UV radiation. POFs help protect balding hair by reducing oxidative damage and slowing down melanin degradation.
Topics: Alopecia; Ultraviolet Rays; Humans; Antioxidants; Hair; Flavonoids; Plant Extracts; Melanins; Keratinocytes
PubMed: 38930941
DOI: 10.3390/molecules29122876 -
Medicina (Kaunas, Lithuania) Jun 2024Medical and public recognition of "long-COVID or post-COVID syndrome", as well as its impact on the quality of life (QoL), is required to better address the disease... (Observational Study)
Observational Study
Medical and public recognition of "long-COVID or post-COVID syndrome", as well as its impact on the quality of life (QoL), is required to better address the disease burden. Objectives: We aimed to describe the persistence of COVID-19 symptoms and QoL among patients at three and twelve months after their discharge from the hospital. We conducted an observational, prospective, and longitudinal analytic study from September 2021 to April 2022. To measure QoL, we used a validated version of the 36-item Short-Form Health Survey (SF-36). We included 68 patients in the study. A total of 54 (79.4%) patients reported at least one persistent symptom at three months vs. 52 (76.4%) at twelve months ( = 0.804). Some persistent symptoms (myalgia, alopecia, and cough) decreased significantly at twelve months (50% vs. 30.9%, 29.4% vs. 13.2%, and 23.5% vs. 7.4%; respectively, = 0.007); in contrast, other persistent symptoms (sleep-wake and memory disorders) were more frequent (5.9% vs. 32.4% and 4.4% vs. 20.6%; respectively, = ≤0.001). Regarding QoL, a statistically significant improvement was observed in some scores over time, = ≤0.037. At twelve months, dyspnea, myalgia, and depression were risk factors associated with a poor physical component summary (PCS), = ≤0.027, whereas anxiety, depression, and fatigue were associated with a poor mental component summary (MCS), = ≤0.015. As the proportion of persistent symptoms at twelve months is high, we suggest that patients must continue under long-term follow up to reclassify, diagnose, and treat new onset symptoms/diseases.
Topics: Humans; COVID-19; Quality of Life; Female; Male; Middle Aged; Prospective Studies; Patient Discharge; Longitudinal Studies; Aged; SARS-CoV-2; Post-Acute COVID-19 Syndrome; Adult; Myalgia; Time Factors; Cough; Alopecia
PubMed: 38929561
DOI: 10.3390/medicina60060944 -
International Journal of Molecular... Jun 2024Aging (senescence) is an unavoidable biological process that results in visible manifestations in all cutaneous tissues, including scalp skin and hair follicles....
Aging (senescence) is an unavoidable biological process that results in visible manifestations in all cutaneous tissues, including scalp skin and hair follicles. Previously, we evaluated the molecular function of adenosine in promoting alopecia treatment in vitro. To elucidate the differences in the molecular mechanisms between minoxidil (MNX) and adenosine, gene expression changes in dermal papilla cells were examined. The androgen receptor (AR) pathway was identified as a candidate target of adenosine for hair growth, and the anti-androgenic activity of adenosine was examined in vitro. In addition, ex vivo examination of human hair follicle organ cultures revealed that adenosine potently elongated the anagen stage. According to the severity of alopecia, the ratio of the two peaks (terminal hair area/vellus hair area) decreased continuously. We further investigated the adenosine hair growth promoting effect in vivo to examine the hair thickness growth effects of topical 5% MNX and the adenosine complex (0.75% adenosine, 1% penthenol, and 2% niacinamide; APN) in vivo. After 4 months of administration, both the MNX and APN group showed significant increases in hair density (MNX + 5.01% ( < 0.01), APN + 6.20% ( < 0.001)) and thickness (MNX + 5.14% ( < 0.001), APN + 10.32% ( < 0.001)). The inhibition of AR signaling via adenosine could have contributed to hair thickness growth. We suggest that the anti-androgenic effect of adenosine, along with the evaluation of hair thickness distribution, could help us to understand hair physiology and to investigate new approaches for drug development.
Topics: Alopecia; Humans; Male; Receptors, Androgen; Adenosine; Hair Follicle; Signal Transduction; Minoxidil; Female; Animals; Hair
PubMed: 38928239
DOI: 10.3390/ijms25126534 -
Journal of the European Academy of... Jun 2024
PubMed: 38925559
DOI: 10.1111/jdv.20197 -
Skin Research and Technology : Official... Jul 2024MicroRNAs (miRNAs) are small RNA molecules that play a regulatory role in various biological processes by acting as intracellular mediators. They hold great potential as...
BACKGROUND
MicroRNAs (miRNAs) are small RNA molecules that play a regulatory role in various biological processes by acting as intracellular mediators. They hold great potential as therapeutic agents for targeting human disease pathways; however, there is still much to be uncovered about their mechanism of gene regulation. Alopecia areata (AA) is a commonly occurring inflammatory condition characterized by the infiltration of T cells that specifically target the anagen-stage hair follicle. The limited understanding of its precise cellular mechanism may be the reason behind the scarcity of effective treatments for AA.
AIM
The significance and function of hsa-miR-193a-5p as a genetic marker for AA and its potential influence on the advancement of the disease.
SUBJECTS AND METHODS
A case-control study comprised 77 individuals diagnosed with AA who were matched with 75 healthy controls. In order to measure the expression of miR-200c-3p in both groups, the real-time PCR technique was utilized. The prediction of suitable genes for hsa-miR-193a-5p, as well as the identification of pathways and gene-gene interactions, were carried out using bioinformatic tools.
RESULTS
The levels of hsa-miR-193a-5p expression were notably elevated in AA patients in comparison to healthy controls. Our prediction suggests that the involvement of hsa-miR-193a-5p in the development of AA is significant due to its influence on the inositol phosphorylation pathway and the Phosphatidylinositol signaling system, achieved through its direct impact on the IPPK gene.
CONCLUSION
For the first time, our study demonstrates the significant over-expression of a new miRNA, hsa-miR-193a-5p, in the blood of AA patients compared to controls, and highlights its impact on the IPPK gene and the inositol phosphorylation and Phosphatidylinositol signaling pathways, suggesting a potential therapeutic role for hsa-miR-193a-5p in AA.
Topics: Humans; Alopecia Areata; MicroRNAs; Male; Case-Control Studies; Female; Adult; Inositol; Middle Aged; Young Adult; Genetic Markers; Phosphotransferases (Alcohol Group Acceptor)
PubMed: 38925555
DOI: 10.1111/srt.13800 -
Actas Dermo-sifiliograficas Jun 2024
PubMed: 38925452
DOI: 10.1016/j.ad.2024.06.004