A Novel Injectable Polypeptide Nanoparticle Encapsulated siRNA Targeting TGF-β1 and COX-2 for Localized Fat Reduction II: Phase I Clinical Trial.

Background: Rising demand for non-invasive body contouring is driven by aesthetics and the obesity epidemic. Deoxycholic acid (DCA) is the only FDA-approved injectable for fat reduction but can cause side effects and significant local skin reactions (LSR). RNA interference, using small interfering RNA (siRNA) molecules, offers targeted fat reduction by silencing genes involved in fat maintenance.

The Therapeutic Role of Genistein in Perimenopausal and Postmenopausal Women.

Objective: We sought to review the biology and clinical benefits of genistein, a plant-derived isoflavone with emphasis on perimenopausal and postmenopausal women. The focus is on assessing its impact on skin health and aesthetics as well as bone density and cardiovascular and metabolic functions.

Methods: This narrative review used PubMed to collect studies relating to the biology and clinical effects of genistein on postmenopausal signs and symptoms, including bone density loss, metabolic issues and symptoms, and skin aging.

Novel injectable polypeptide nanoparticle encapsulated siRNA targeting TGF-β1 and COX-2 for localized fat reduction I: Preclinical in vitro and animal models.

Background: Obesity and localized fat accumulation continue to drive the demand for minimally invasive body contouring technologies including injectable compounds for local fat reduction. siRNA offers a potential for an injectable to specifically target and silence genes involved in adipogenesis with minimal inflammatory side effects.

Aims: This study evaluates the efficacy of STP705, an injectable containing siRNA encapsulated within histidine-lysine polypeptide (HKP) nanoparticles targeting transforming growth factor β1 (TGF-β1) and cyclooxygenase-2 (COX-2), crucial mediators in adipocyte differentiation and fat retention, using in vitro, porcine, and murine models.

A cross-sectional content quality analysis of information in TikTok videos on "Dermarolling (Roller Microneedling)".

Background: TikTok is one of the fastest-growing social media platform, and its short-form videos have become a widely used source of health information. "Dermarolling" is a form of roller microneedling often practiced at home, and patients may be using TikTok to inform their decision to pursue this treatment and their practice of it.

Aims: This study assessed the informational content quality, source, and engagement of TikTok dermarolling videos to highlight potentially harmful social media trends.

MDM2/MDMX inhibition by Sulanemadlin synergizes with anti-Programmed Death 1 immunotherapy in wild-type p53 tumors.

Immunotherapy has revolutionized cancer treatment but its efficacy depends on a robust immune response in the tumor. Silencing of the tumor suppressor p53 is common in tumors and can affect the recruitment and activation of different immune cells, leading to immune evasion and poor therapy response. We found that the p53 activating stapled peptide MDM2/MDMX inhibitor Sulanemadlin (ALRN-6924) inhibited p53 wild-type cancer cell growth and .

Bleeding Reversal With Antifibrinolytics or Cryoprecipitate Following Thrombolysis for Acute Ischemic Stroke: A Case Series.

Patients who develop an intracerebral hemorrhage (ICH) following thrombolysis in acute ischemic stroke (AIS) have a mortality rate as high as 50%. Treatment options include blood products, such as cryoprecipitate, or antifibrinolytics, such as tranexamic acid (TXA) or ε-aminocaproic acid (EACA). Current guidelines recommend cryoprecipitate first-line despite limited data to support one agent over another.

Treatment Options for Onychomycosis: Efficacy, Side Effects, Adherence, Financial Considerations, and Ethics.

Background: Onychomycosis is a fungal infection of the nail unit that affects a large patient population globally. Onychomycosis, or tinea unguium, has a benign chronic clinical course; however, it can cause complications in certain patient populations suffering from diabetes and peripheral vascular disease. As nails grow slowly, onychomycosis requires a lengthy treatment plan, and choosing appropriate treatments can be challenging.

Efficacy and Safety of LetibotulinumtoxinA in the Treatment of Moderate and Severe Glabellar Lines in Females 35 to 50 Years of Age: Post Hoc Analyses of the Phase 3 Clinical Study Data.

Background: Botulinum toxin type A (BoNT-A) injections continue to be widely used as a common treatment for both males and females. According to a recent survey conducted by the International Society of Plastic Aesthetic Surgeons, the majority of patients receiving these injections are females between the ages 35 and 50.

Objectives: A post hoc analysis was conducted to examine whether there were variances in the effectiveness and safety of letibotulinumtoxinA for treating vertical glabellar lines between the broader female study population and a particularly defined group of female participants aged 35 to 50.

LetibotulinumtoxinA Attenuates the Psychological Burden of Glabellar Lines and Is Associated With High Subject Satisfaction in Phase 3 Clinical Trials.

Background: Hyperfunctional glabellar frown lines can transmit facial miscues that adversely affect emotional communication, increase perceptions of age, and diminish self-esteem.

Objective: To evaluate the efficacy of letibotulinumtoxinA in mitigating the negative psychological impact associated with moderate to severe glabellar lines and to assess subject satisfaction with treatment outcome in the BLESS phase 3 clinical trials.

Materials And Methods: Baseline and posttreatment assessments were made using validated subject-administered instruments: Modified Skindex-16 Glabellar Line Quality of Life (GL-QoL) Scale, Facial Assessment and Cosmetic Evaluation Questionnaire (FACE-Q) Appraisal of Lines Between Eyebrows Scale, FACE-Q Age Appraisal Visual Analog Scale, and FACE-Q Satisfaction with Outcome Scale.

Design-rules for stapled peptides with in vivo activity and their application to Mdm2/X antagonists.

Although stapled α-helical peptides can address challenging targets, their advancement is impeded by poor understandings for making them cell permeable while avoiding off-target toxicities. By synthesizing >350 molecules, we present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects. Key insights include a clear correlation between lipophilicity and permeability, removal of positive charge to avoid off-target toxicities, judicious anionic residue placement to enhance solubility/behavior, optimization of C-terminal length/helicity to enhance potency, and optimization of staple type/number to avoid polypharmacology.

Utilizing CD44v6 and V600EBRAF-mutation for in vitro targeted combination therapy of thyroid carcinomas.

Aim: The aim of this study was to assess the feasibility of targeted therapy of thyroid carcinoma, first exploring potential targets BRAF, EGFR and CD44v6 in patient material through immunohistochemistry and mutation analysis.

Materials And Methods: A patient cohort (n = 22) consisting of seven papillary (PTC), eight anaplastic (ATC) and seven follicular (FTC) thyroid carcinomas were evaluated. Additionally, eight thyroid carcinoma cells lines were analyzed for CD44v6-expression and sensitivity to the multi-kinase inhibitor sorafenib (Nexavar®), which targets numerous serine/threonine and tyrosine kinases, including the Raf family kinases.

Selection, characterization and in vivo evaluation of novel CD44v6-targeting antibodies for targeted molecular radiotherapy.

Molecular radiotherapy combines the advantages of systemic administration of highly specific antibodies or peptides and the localized potency of ionizing radiation. A potential target for molecular radiotherapy is the cell surface antigen CD44v6, which is overexpressed in numerous cancers, with limited expression in normal tissues. The aim of the present study was to generate and characterize a panel of human anti-CD44v6 antibodies and identify a suitable candidate for future use in molecular radiotherapy of CD44v6-expressing cancers.

Cryolipolysis in the United States-Review of the clinical data.

Background: Noninvasive body contouring is becoming more popular in the United States as an alternative to liposuction. The most popular of these methods, cryolipolysis, uses precisely controlled cooling to reduce focal adiposities. The number of cryolipolysis procedures performed annually has experienced rampant growth in United States markets, and the indications have likewise diversified.

Real-world outcomes of 18,186 metastatic solid tumor outpatients: Baseline blood cell counts correlate with survival after immune checkpoint inhibitor therapy.

Background: Patient survival in advanced/metastatic melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) has improved with immune checkpoint inhibitors (ICI). Biomarkers' role in prognosis and treatment has been limited by conflicting trial results.

Methods: This retrospective, observational study analyzed baseline demographic, clinical, laboratory, and treatment data versus outcomes of The US Oncology Network adult outpatients.

p53 stabilisation potentiates [Lu]Lu-DOTATATE treatment in neuroblastoma xenografts.

Purpose: Molecular radiotherapy is a treatment modality that is highly suitable for targeting micrometastases and [Lu]Lu-DOTATATE is currently being explored as a potential novel treatment option for high-risk neuroblastoma. p53 is a key player in the proapoptotic signalling in response to radiation-induced DNA damage and is therefore a potential target for radiosensitisation.

Methods: This study investigated the use of the p53 stabilising peptide VIP116 and [Lu]Lu-DOTATATE, either alone or in combination, for treatment of neuroblastoma tumour xenografts in mice.

Enhanced Therapeutic Effects of Lu-DOTA-M5A in Combination with Heat Shock Protein 90 Inhibitor Onalespib in Colorectal Cancer Xenografts.

Carcinoembryonic antigen (CEA) has emerged as an attractive target for theranostic applications in colorectal cancers (CRCs). In the present study, the humanized anti-CEA antibody hT84.66-M5A (M5A) was labeled with Lu for potential CRC therapy.

Proteogenomic insights suggest druggable pathways in endometrial carcinoma.

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity.

Complementarity-determining region clustering may cause CAR-T cell dysfunction.

Chimeric antigen receptor (CAR)-T cell therapy is rapidly advancing as cancer treatment, however, designing an optimal CAR remains challenging. A single-chain variable fragment (scFv) is generally used as CAR targeting moiety, wherein the complementarity-determining regions (CDRs) define its specificity. We report here that the CDR loops can cause CAR clustering, leading to antigen-independent tonic signalling and subsequent CAR-T cell dysfunction.

Evaluating the safety and efficacy of aminolevulinic acid 20% topical solution activated by pulsed dye laser and blue light in the treatment of facial cutaneous squamous cell carcinoma in situ.

Background: Squamous cell carcinoma (SCC) is the second most common cutaneous malignancy, after basal cell carcinoma (BCC). Photodynamic therapy (PDT) involves converting a photosensitizer to reactive oxygen intermediates, which preferentially bind to hyperproliferative tissue. The most commonly used photosensitizers are methyl aminolevulinate and aminolevulinic acid (ALA).