Paracoccidioidomycosis (PCM), the most prevalent systemic mycosis in Brazil, is caused by dimorphic fungi of the genus Paracoccidioides and is acquired primarily through inhalation. PCM is associated with a high mortality, particularly among men living in rural areas. This case report describes a 47-year-old man with osteocutaneous involvement diagnosed by biopsy and direct fungal examination. The osseous form of PCM is rare and should be differentiated from other infections and neoplasms. Management involves prolonged antifungal therapy and follow-up for at least two years. This case highlights the diagnostic value of dermatological assessments in atypical presentations of PCM.

Delayed gastric conduit emptying (DGCE) is a common functional syndrome after esophagectomy. The clinical phenotype is characterized by regurgitation, reflux, and the inability to meet caloric requirements by oral intake. Diagnosis and cause-directed therapy are often challenging because of variable underlying pathomechanisms. Against this background and based on our clinical experience, we propose a classification that categorizes DGCE according to the predominant case-specific pathophysiology: Class I: functional-DGCE due to impaired antro-pyloric motilityClass II: conduit-related-DGCE caused by specific patho-anatomical features of the conduitClass III: hiatal-DGCE resulting from mechanical obstruction at the diaphragmatic hiatusClass IV: other-Other causes of DGCE at or distal to the pylorus (e.g. luminal occlusion, intestinal adhesions or peritoneal carcinomatosis) We believe that this classification has the potential to promote a better understanding of the symptom spectrum of DGCE and to facilitate cause-oriented, focused treatment. Moreover, we are convinced that a structured definition of DGCE according to pathophysiology will improve the comparability of different patient cohorts and thus promote future collaborative research.

The nanomedicine field continues to gain momentum, with several groundbreaking clinical trials underway. However, despite the promise of advanced antifouling nanoparticles incorporating poly(ethylene glycol)-a key component in the development of COVID-19 vaccines-the clinical translation of nanomedicine remains limited. This is primarily due to the relatively low delivery efficacy, with passive targeting relying on the enhanced permeability and retention effect, and active targeting leading to only modest improvements in target tissue accumulation. Improving the targeting, biocompatibility, and functionality of nanoparticles has the potential to create more effective, personalized, and minimally invasive therapies. This review aims to highlight the rise of a previously unidentified order of immune-minded nanomaterials and explores how mechanobiological principles and biomechanical nanotools are revolutionizing our understanding of nano-bio interactions in relation to disease. By considering mechanical properties such as stiffness, surface topology, and behavior under physiological flow conditions, researchers can better engineer nanoparticles for improved therapeutic outcomes.

Extracellular vesicles (EVs) demonstrate immense potential as naturally derived carriers of active therapeutics. To maximize their capacity, it is crucial to develop effective methods for manipulating cargo and ensuring scalability. To address this challenge, we propose that protein-free mRNA granule-like structures, named gene-encoded nanoparticle RNA for inducing superior EVs (GENRISE), can function as active translational sponge and as transient subcellular compartments. The overexpression of proteins in proximity to RNA assemblies stimulates parental cells to release excess exogenous proteins in induced superior EVs (iSEVs). The iSEV system enables the single-module-based enrichment of exogenous cargo in EVs with scalable manufacturing. By harnessing mass-produced iSEVs induced by GENRISEs, encoding an antigenic peptide, we have successfully demonstrated target-specific in vivo cancer immunotherapy. These findings suggest that the emerging iSEV platform shows considerable potential for biomedical applications by enabling the controlled production of cargo-specific EVs.

Psoriasis (Pso) is a chronic inflammatory skin disease driven by T helper 17 (T_H17) cells, with several clinical subtypes. While self-reactive immune responses have been observed, the role of autoantigens in Pso remains unclear. Using immunopeptidomics, we identified serpin family B member 3 (SERPINB3) and SERPINB4 as candidate autoantigens in Pso skin. In a mouse model, the SERPINB3 ortholog Serpinb3b enhanced inflammation, promoted tissue-resident memory T cells, and skewed immunity toward a T_H2 phenotype. In humans, SERPINB3 reactivity was specifically associated with "eczematized psoriasis" (EczPso), a subtype marked by T_H2/T_H17 immune signatures. SERPINB3 protein was enriched in EczPso lesions and highly secreted by keratinocytes under combined T_H2/T_H17 stimulation. Lesional T cells from EczPso-but not from eczema or classical plaque Pso-proliferated in response to SERPINB3 and induced EczPso-like features in a skin model. Our findings identify SERPINB3 as an autoantigen driving a distinct Pso subtype, supporting more precise diagnosis and therapy.

Mitochondrial division and fusion are critical regulators of cancer cell metabolism, proliferation, survival, metastasis, and drug resistance. Division promotes tumor development by reprogramming energy metabolism, whereas its inhibition can suppress tumor growth and metastasis. The mechanochemical GTPase DRP1, a key mediator of mitochondrial division, has emerged as a promising therapeutic target. Mitochondrial cristae also contribute to cancer progression by modulating metabolic reprogramming and oncogenic signaling. Targeting these processes may stimulate anti-tumor innate immune responses through the release of mitochondrial DNA into the cytoplasm. A deeper understanding of tumor-specific mitochondrial membrane structures and dynamics could therefore reveal novel intervention strategies and guide precision cancer therapies.

This study aimed to develop a versatile aptamer-conjugated, photothermal responsive camptothecin (CPT)-loaded chitosan-bimetallic (Pd/Au) nanoparticles (Ap-CH-CPT-Pd/Au NPs) to enhance cytotoxicity in lung cancerous NCI-H446 and H1299 cells. The CH-CPT-Pd/Au NPs exhibited polydispersity with a diameter of 33.87 ± 2.23 nm. FTIR investigation revealed the presence of chitosan and camptothecin in chitosan-camptothecin-palladium/gold nanoparticles. The 2θ of CH-CPT-Pd/Au corresponded to chitosan and palladium/gold. The Ap-CH-CPT-Pd/Au NPs (180 μg/mL) subjected to near-infrared (NIR) treatment elevated the temperature to over 50 °C. The optimum CPT concentration was 0.075% in CH-CPT-Pd/Au, demonstrating a hydrodynamic diameter of 113.12 ± 16.78 nm, a drug loading efficiency (DLE) of 10.89 ± 0.53%, and a drug encapsulation efficiency (DEE) of 63.97 ± 4.21%. A CPT release rate of 7.23 ± 3.25% was recorded at pH = 5.4 after 74 h. In addition, NIR+Ap-CH-CPT-Pd/Au NPs exhibited negligible toxicity to red blood cells (RBCs). However, enhanced cytotoxicity in NCI-H446 and H1299 lung carcinoma cells is achieved through the induction of oxidative stress-mediated apoptosis.

Poorly differentiated thyroid carcinoma (PDTC) is a rare thyroid cancer with aggressive clinical course and peculiar clinical/pathological characteristics but lacking effective therapeutic options, when surgery is not curative. We aimed at the molecular characterization of PDTC with a specific focus on the identification of potential therapeutic targets. A series of PDTC cases was selected from a multi-institutional network. Fifty-nine samples underwent wide targeted DNA and RNA next-generation sequencing (NGS) testing and immunohistochemical analysis for mismatch repair (MMR) proteins. Gene fusion analysis was enriched by 25 additional samples. Prevalence of MMR protein loss was 11.9%. The most prevalent mutations were in NRAS (25%) and TP53 (25%), mutually exclusive. TERT promoter (TERTp) mutations were detected in 19.6% of cases (10/51). NRAS-mutated cases were enriched for mutations in genes belonging to the same pathway. TP53-mutated samples lacked TERTp co-mutations, but were associated with mutations in PTEN and in genes related to MMR system and/or loss of MMR proteins. TERTp mutations were the most prevalent alterations (28%, 7/25) in a third group that lacked NRAS or TP53 mutations. Four cases harbored gene fusions, including two cases harboring the TBL1XR1::PIK3CA fusion that has never been reported in thyroid cancer, so far. In conclusion, PDTC may be genomically segregated in subgroups with specific molecular characteristics. Overall, targetable gene fusions have a prevalence of 9% (4/42). Moreover, 47% of cases are potential candidates for individualized target therapies since they harbor mutations in genes coding for potentially targetable molecules and/or have defects in the MMR system.

The use of targeted drug delivery systems to accumulate medications in cancer cells, along with the simultaneous application of multiple drugs, can facilitate the administration of optimal doses, leading to more efficient treatment as well as reduced side effects. We fabricated zirconium-based UiO-66-NH₂ metal-organic framework (MOF) nanoparticles (NPs) with folic acid (FA) conjugated onto their surface for targeted delivery of doxorubicin (DOX), and smart drug release within tumor cells. Following the physicochemical characterization of the prepared NPs, the drug release profile was investigated in simulated media with pH 5.4 and 7.4. Subsequently, the internalization and anticancer effects of the NPs were evaluated in HT-29 and HEK-293 cells to assess their selectivity. Simultaneous treatment of HT-29 cells with FA-decorated NPs and hydroxychloroquine (HCQ), an autophagy inhibitor, was performed to sensitize cancer cells. The synergistic effects of combined treatment were assessed through MTT assay and autophagy flux detection. UiO-66-NH₂-FA@DOX NPs with a surface area of 323 m²/g and a high loading capacity of 36.25% showed a pH-dependent release with a substantial increase in acidic condition. Higher uptake of targeted NPs in HT-29 cells led to higher cytotoxicity and apoptosis. The combination of HCQ and targeted NPs increased cytotoxic effects against HT-29 cells compared to treatment with targeted NPs alone. Acridine orange staining revealed different patterns of autophagy flux in the co-administered drug groups. This study suggests that our DOX-loaded targeted nanocarrier enhances the therapeutic efficacy through localized drug delivery and reduced potential side effects compared to conventional DOX treatment. Its combination with HCQ may offer a promising strategy for safer and more effective colorectal cancer therapy by enabling dose reduction of both agents. However, further in vivo studies are necessary to validate these findings.

Triple-negative breast cancer (TNBC) is an aggressive and clinically challenging subtype defined by the absence of estrogen receptor, progesterone receptor, and HER2 amplification, resulting in poor prognosis and limited therapeutic options. Targeting alternative molecular pathways is urgently needed to overcome resistance and improve patient outcomes. CD147 has emerged as surface marker associated with tumor progression and immune evasion. In this study, CD147 and MHC class I-a key inhibitory ligand for natural killer cells-were analyzed in breast cancer cell lines (MCF7, MDA-MB-453, MDA-MB-231, and HCC38) using flow cytometry. The therapeutic efficacy of a humanized anti-CD147 monoclonal antibody (HuM6-1B9) was evaluated for its capacity to potentiate antibody-dependent cellular cytotoxicity (ADCC). HuM6-1B9 demonstrated the strong binding to MDA-MB-231 (K_D = 4.982 nM) and HCC38 (K_D = 4.523 nM), which are representative TNBC cell lines. In 3D spheroid models, HuM6-1B9 significantly enhanced PBMC-mediated ADCC, leading to a marked reduction in TNBC spheroid viability. Co-culture of CFSE-labeled MDA-MB-231 and HCC38 cells with primary NK cells confirmed robust ADCC, achieving 50% and 70% cytotoxicity, respectively, despite high MHC class I expression. Live-cell imaging demonstrated caspase-3/7 activation consistent with apoptosis in NK-targeted tumor cells, while CD107a degranulation and IFN-γ secretion confirmed the functional contribution of HuM6-1B9 to ADCC enhancement. Importantly, HuM6-1B9 did not promote migration or invasion in MDA-MB-231 cells, supporting its safety profile regarding metastasis. Collectively, these findings establish HuM6-1B9 as a promising immunotherapeutic candidate that overcomes immune resistance and selectively eliminates TNBC cells through ADCC without enhancing metastatic potential. By integrating mechanistic assays of NK cytotoxicity, apoptosis, and 3D tumor spheroids, this study provides clinically relevant insights underscoring the translational potential of HuM6-1B9 in TNBC immunotherapy.