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Coumarin and Curcumin-Metal Complexes as Next-Generation Photosensitizers in Cancer Photodynamic Therapy.

To explore the emerging role of natural ligands, specifically coumarin and curcumin, and their coordination with the transition metals ruthenium (Ru) and iridium (Ir) as photosensitizers (PSs) in photodynamic therapy (PDT) for cancer. This highlights the integration of natural compounds and transition metals to overcome limitations in photophysical properties, hypoxia tolerance, and clinical translation. Regarding PDT oncology, this examines an immunological effect on Ru/Ir complexes and natural ligand-metal hybrids. They induce immunogenic cell death (ICD) through reactive oxygen species (ROS

CD4 and CD8 T-cell lymphocytes from penile squamous cell carcinoma tumors are more differentiated with higher PD-1 expression compared to lymphocytes in peripheral circulation.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is the commonest malignancy of the penis, with a higher incidence and poor treatment outcomes in developing countries. T-cell phenotypes have been shown to identify patients who may respond favorably to immune therapy, and also associate with treatment outcomes. This study aimed to determine and compare the tumor and peripheral blood T-cell phenotypes of individuals with PSCC, and whether factors such as smoking and presence of HPV associate with these T-cell phenotypes. METHODS: We conducted a prospective cross-sectional study at the Universi

Peptide-Based Catalysts Reach the Outer Sphere through Remote Desymmetrization and Atroposelectivity.

Nature's catalytic machinery has provided endless inspiration for chemists. While the enzymatic ideal has yet to be fully realized, the field has made tremendous strides toward synthetic, small-molecule catalysts for a wide array of transformations, often drawing upon biological concepts in their design. One strategy that has been particularly influenced by enzymology is peptide catalysis, wherein oligopeptides are implemented as chiral catalysts in synthetically relevant reactions. The fundamental goal has been to mimic enzymatic active sites by taking advantage of secondary structures that a

Efficacy of a monovalent (D614) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, multi-country study.

BACKGROUND: The literature on first generation COVID-19 vaccines show they were less effective against new SARS-CoV-2 variants of concern including Omicron (BA.1, BA.2, BA.4 and BA.5 subvariants). New vaccines developed against variant strains may provide cross-protection against emerging variants when used as boosters and facilitate vaccination across a range of countries, healthcare settings and populations. However, there are no data on such vaccines when used as a primary series. METHODS: A global Phase 3, multi-stage efficacy study (NCT04904549) among adults (≥18 years) was conducted in

Safety and immunogenicity of a live attenuated influenza H5 candidate vaccine strain A/17/turkey/Turkey/05/133 H5N2 and its priming effects for potential pre-pandemic use: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The emergence of highly pathogenic avian influenza H5N1 viruses has raised concerns about their pandemic potential. Vaccination is the most effective way of preventing influenza. In this study, we investigated the safety and immunogenicity of an avian H5N2 live attenuated influenza vaccine (LAIV H5N2) in healthy Thai adults and its priming immune responses with an H5N1 inactivated vaccine boost. METHODS: This study was done at the Vaccine Trial Centre at Mahidol University, Bangkok, Thailand and was divided into two parts. Part 1 consisted of a randomised, double-blind, placebo-co

The Safety of Social Media Instigated Visitation to National Parks in New South Wales, Australia: Insights From a Population Representative Sample.

ISSUE ADDRESSED: The integration of social media, smartphone technology and the widespread sharing of images has reshaped tourism, sparking new trends such as selfie-tourism and social media-driven travel. National parks, offering scenic and pristine landscapes, have become prime destinations for these pursuits. The popularity of platforms like Instagram and Facebook, combined with the influence of travel-focused social media personalities, has inspired a wave of visitors seeking "selfie-worthy" locations. However, this shift in visitation motives has raised environmental and safety concerns:

The understated issue of caregiver anxiety for pediatric surgical hospital admissions: opening the blindfolds.

KEY MESSAGE: Hospitalization is a nerve-wrecking experience for patients and their families (Lam et al. in Int J Nurs Stud 43:535-545, 2006). The financial burden of hospitalization is the prime perpetrator, however, multiple other factors also contribute significantly to the underlying problem which can be eliminated by efforts of the doctors and other healthcare workers and by modifying the hospital policies (Bassett et al. in J Hosp Med 15:652-658, 2020). We can reduce the number of outpatient visits and switch to telemedicine for rescheduling the cases. The pre-anaesthetic clearance and al

Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study.

BACKGROUND: Bivalent oral poliovirus vaccine (bOPV; types 1 and 3) is expected to replace trivalent OPV (tOPV) globally by April, 2016, preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus. Because data are needed on sequential IPV-bOPV schedules, we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants. METHODS: We did a randomised, controlled, open-label, non-inferiority tria

Pharmacokinetics and pharmacodynamics in clinical use of scopolamine.

The alkaloid L-(-)-scopolamine [L-(-)-hyoscine] competitively inhibits muscarinic receptors for acetylcholine and acts as a nonselective muscarinic antagonist, producing both peripheral antimuscarinic properties and central sedative, antiemetic, and amnestic effects. The parasympatholytic scopolamine, structurally very similar to atropine (racemate of hyoscyamine), is used in conditions requiring decreased parasympathetic activity, primarily for its effect on the eye, gastrointestinal tract, heart, and salivary and bronchial secretion glands, and in special circumstances for a CNS action. Ther

[Buprenorphine abuse: high dose intravenous administration of buprenorphine].

BACKGROUND: In France, actually, around 70 000 drug addicts are treated with buprenorphine available as sublingual tablets. Clinical studies have demonstrated the clinical efficacity of buprenorphine for opiate addiction. But, it has been reported that some of them injected buprenorphine. Some inquiries have suggested measured with 10% to 40% injectors. To use buprenorphine tablets for injections have had heavy sanitary consequences (4). OBJECTIVES: To know the use buprenorphine context in our population and to analyse the circumstances and outcomes of buprenorphine injection for drug addicts

Abscopal Effect in Radiation Therapy: The Immune Mechanisms and Clinical Advances.

The abscopal effect is a systemic antitumor response to localized radiotherapy (RT) that has emerged as a central focus in the era of immunotherapy. Clinical evidence demonstrates that local RT can induce regression of distant, nonirradiated metastases, including cases of complete remission. However, the effect remains unpredictable, with marked variation in clinical outcomes ranging from complete regression to paradoxical progression. The mechanistic basis for this heterogeneity and optimal strategies to enhance abscopal effects remain incompletely understood. This review synthesizes current

Recent advances in renal transplantation: antibody-mediated rejection takes center stage.

Overlooked for decades, antibodies have taken center stage in renal transplantation and are now widely recognized as the first cause of allograft failure. Diagnosis of antibody-mediated rejection has considerably improved with identification of antibody-mediated lesions in graft biopsies and advances made in the detection of circulating donor-specific antibodies. Unfortunately, this progress has not yet translated into better outcomes for patients. Indeed, in the absence of a drug able to suppress antibody generation by plasma cells, available therapies can only slow down graft destruction. Th

Nanoparticle Strategies for Bone Metastasis Immunotherapy: Targeting, Immune Reprogramming and Combination Therapy.

Bone metastases remain one of the most clinically devastating complications of advanced cancer, particularly in breast, prostate, and lung malignancies, where they drive pain, fractures, hypercalcemia, and progressive functional decline. Their management is further complicated by a highly immunosuppressive bone microenvironment characterized by osteoclast-driven bone destruction, myeloid cell dominance, impaired antigen presentation, and weak effector T-cell infiltration, all of which limit the activity of conventional immunotherapies. In this setting, nanoparticles are emerging not merely as

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… Moreover, this strategy could augment dendritic cell activation and cross-priming in the bone marrow and draining lymph nodes. … Secondly, the intrinsic signaling from STING or TLR9 functions as a “licensing” signal, transforming immature antigen-presenting cells into proficient cross-priming cells by enhancing MHC and costimulatory molecule expression [ 201 , 203 , 207 ]. …

Dendritic cell biology and its role in tumor immunotherapy.

As crucial antigen presenting cells, dendritic cells (DCs) play a vital role in tumor immunotherapy. Taking into account the many recent advances in DC biology, we discuss how DCs (1) recognize pathogenic antigens with pattern recognition receptors through specific phagocytosis and through non-specific micropinocytosis, (2) process antigens into small peptides with proper sizes and sequences, and (3) present MHC-peptides to CD4+ and CD8+ T cells to initiate immune responses against invading microbes and aberrant host cells. During anti-tumor immune responses, DC-derived exosomes were discovere

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… Cross-presentation and cross-priming Cross-presentation is the process wherein DCs take up, process, and present extracellular antigens via MHC-I molecules to CD8 + T cells. This is also known as cross-priming [ 73 ]. … Only DCs can cross-prime for a cytotoxic CD8 + T cell response [ 62 ]. Particularly, XCR1 + DCs are crucial for cross-presentation and communication between CD4 + and CD8 + T cells in a productive vaccinia virus (VV) infection [ 74 ]. Many factors will infect cross-presentation. …

Breaking Therapy Resistance: An Update on Oncolytic Newcastle Disease Virus for Improvements of Cancer Therapy.

Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus (NDV) as a biological agent with potential to break therapy resistance. This avian virus combines, upon inoculation into non-permissive hosts such as human, 12 described anti-neoplastic effects with 11 described immune stimulatory properties. Fifty years of clinical application of NDV give witness to the high safety profile of this biological agent. In 2015, an important milestone was achieved, namely the succ

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… DCs cross-presenting antigens can either induce an adaptive T cell response (cross-priming) or they can prevent such a response (cross-tolerance), depending on the context of antigen-presentation. While IFN-I facilitates cross-priming [ 97 ], TGF-β facilitates cross-tolerance [ 98 ]. …

Иммунный код мозга: декодирование антигенной презентации на менингеальном-глимфатичном интерфейсе в неврологических расстройствах.

Классический взгляд на иммунную привилегию центральной нервной системы (СНС) эволюционировал от изоляции к регулируемому перекрестному разговору. Перенос церебральных цереброспинных флюидов и менингетических лимфатических сосудов (mLVs) переносят молекулы, полученные из головного мозга, на эмунизированные пограничные ткани и лимфатические узлы шейки матки, где антигенные клетки (APC) декодируют этот молекулярный дренаж в адаптивный иммунитет. Мы настраиваем эту последовательность как код мозга, в котором личность, время, маршрут и клеточный проводник экспортированных антигенов коллективно дикт

Нацеливание микроглиа-Тх17 на петлю питания вперёд для подавления аутоиммунной нейроинфламмации.

Microglia и TH17 являются основными иммунопатогенными клетками в множестве склероза и его животной модели иммунных аспектов, экспериментального аутоиммунного энцефаломиелита (EAE). Хотя исследования выявили различные роли микроглий и TH17 клеток в EAE, остается неясным, может ли микроглия как потенциальные профессиональные антигенопредставляющие клетки активировать и стабилизировать программу воздействия EAE-патогенных клеток TH17 в vivo; и если да, то может ли TH17, в свою очередь, усилить активное состояние микроглии. Наши данные показывают в целом ряде моделей мыши, включая активные/пассивн

Использование реальных доказательств в США. Управление по контролю за продуктами питания и лекарственными препаратами и Европейское агентство по лекарственным препаратам утверждают онкологические продукты, поддерживаемые односторонними испытаниями (Advisory and Drug Argency and the European Medicals Agency (European Medicals Agency)2022-2025).

ВВЕДЕНИЕ: Усилился интерес регулирующих органов к реальным доказательствам (РВЭ) в дополнение к односторонним испытаниям (САТ) в области онкологии, однако по-прежнему отсутствует полное понимание того, как Управление по контролю за продуктами питания и лекарствами (ДПП) и Европейское агентство по медицине (ЕМА) оценивают такие доказательства. ЦЕЛЬ: Всеобъемлющая оценка недавних решений по онкологии, в которых СТА поддерживаются РВЭ, с описанием обратной связи по вопросам нормативного регулирования, методологических подходов, роли РВЭ в процессе принятия решений. Мы рассмотрели новые прикладные

Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results.

Elranatamab is a humanized B-cell maturation antigen (BCMA)-CD3 bispecific antibody. In the ongoing phase 2 MagnetisMM-3 trial, patients with relapsed or refractory multiple myeloma received subcutaneous elranatamab once weekly after two step-up priming doses. After six cycles, persistent responders switched to biweekly dosing. Results from cohort A, which enrolled patients without prior BCMA-directed therapy (n = 123) are reported. The primary endpoint of confirmed objective response rate (ORR) by blinded independent central review was met with an ORR of 61.0% (75/123); 35.0% ≥complete respon

Regulatory Convergence in Cell and Gene Therapy: Harmonizing Quality, CMC, and Approval Pathways Across the FDA, EMA, PMDA, and Emerging Markets.

Cell and gene therapies (CGTs) have progressed from proof of concept to an established commercial pipeline, yet global translation remains constrained by fragmented regulatory frameworks; heterogeneous Chemistry, Manufacturing, and Controls (CMC) requirements; and divergent approval pathways. This narrative review compares CGT quality, CMC, and approval-pathway regulation across the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and Japan's Pharmaceuticals and Medical Devices Agency (PMDA), together with five emerging-market agencies: Brazil, Russia, India, China, and