Patients with densely innervated tumors suffer with poor outcomes, thus identifying them could define a cohort that could benefit from aggressive treatments. Most cases and deaths from ovarian cancer are associated with high-grade serous ovarian carcinoma (HGSOC). We immunohistochemically analyzed the histological subtypes of ovarian cancer (high-grade serous, low-grade serous, clear cell, mucinous, and endometrioid) for nerves; only HGSOCs were densely innervated. We previously defined that tumor-released small extracellular vesicles (sEVs) recruit nerves to the tumor bed and thus tested whether the difference in nerve infiltration amongst ovarian cancers was associated with sEVs. Using an in vitro neurite outgrowth assay, we found that HGSOC sEVs harbored robust neurite outgrowth activity. Importantly, sEVs from fallopian tube cell lines (the primary cell of origin of HGSOC) predominantly lacked this activity. Implantation of a syngeneic mouse model of HGSOC into transgenic mice lacking tumor-infiltrating nerves slowed tumor growth, sensitized disease to carboplatin, and improved survival. Consistent with this, we show that recurrent, treatment-resistant disease in patients is significantly more innervated than its matched naïve (untreated) malignancy. Taken together, these data identify dense nerve infiltration of HGSOCs and show that innervation contributes to treatment resistance.

Ischemia-reperfusion injury remains a major challenge in modern regenerative medicine due to its complex mechanisms, lack of effective therapies, and persistent constrains to translating new interventions from bench to bedside. Currently, there are no FDA-approved drugs that directly target ischemia-reperfusion injury, highlighting a substantial therapeutic gap. While restoring blood flow is vital for salvaging ischemic tissue, the reperfusion process paradoxically triggers additional cellular damage. The clinical significance and complexity of ischemia-reperfusion injury underscore an urgent need for mechanistically targeted therapeutic approaches. Recent research has identified pivotal molecular targets-PHLDA1, SIRT6, PKM2, and ubiquitin-specific proteases (USPs)-that play key roles in modulating cellular responses such as oxidative stress, inflammation, metabolism, apoptosis, autophagy, ferroptosis, and blood-brain barrier dysfunction during ischemia reperfusion injury. Advances in understanding these mechanisms offer promising strategies for developing novel interventions to mitigate tissue damage and improve patient outcomes. This review critically examines these molecular targets, detailing recent advances and outlining future directions in ischemia reperfusion injury research.

Mesenchymal stem cells (MSCs) migrate to injured tissues, aiding tissue repair, remodeling, and wound healing. As tumors are often considered to have traits of "injured tissues," MSCs are recruited to tumor microenvironments where they can have pro- and antitumorigenic influences. This study assesses whether human mesenchymal stem cells (hMSCs) of shared ancestry exhibit similar tumorigenic properties. Bone marrow-derived (hBM-MSCs) and umbilical cord-derived (hUC-MSCs) MSCs embedded in collagen are cultured in conditioned media from lung adenocarcinoma (A549) cells to mimic the extracellular matrix and soluble cues of the cancer microenvironment. Cell viability, proliferation, and immunofluorescence analyses evaluate MSC behavior under these conditions. Further, A549 cells are exposed to conditioned media from cancer-stimulated MSCs to simulate indirect co-culture, and their response is assessed through viability, immunofluorescence, and flow cytometric analysis. Results show increased viability and proliferation of hBM-MSCs, morphological changes, and elevated alpha-smooth muscle actin expression, suggesting a transition toward cancer-associated fibroblasts. In contrast, hUC-MSCs display reduced viability and no morphological alterations. Conditioned media from cancer-exposed hUC-MSCs induce apoptosis in A549 cells, whereas hBM-MSCs support A549 growth. These findings demonstrate that, despite their common origin, hUC-MSCs and hBM-MSCs exhibit opposing responses to tumor cues and influence lung cancer cell behavior differently.

Antimicrobial Photodynamic Therapy (aPDT) has become a potential alternative for treating multidrug‐resistant bacterial skin infections, such as those caused by methicillin‐resistant Staphylococcus aureus (MRSA), which are at high risk in aging individuals. One of the main components of aPDT is an agent known as a photosensitizer (PS). Some plants with high flavonoid content are reported as PS. In the genus Passiflora, flavonoids are predominant, but their photosensitizing activity has yet to be described. This study investigates the photosensitizing potential of extracts from Passiflora edulis, Passiflora alata, and Passiflora cincinnata. The butanolic fraction of P. cincinnata undergoes in vivo evaluation against intradermal MRSA infection in a senescent murine model (C57BL/6). In vitro assays determine the photoactivatable concentrations and their cytotoxicity. In vivo, MRSA‐infected mice are divided into control, P. cincinnata‐treated, and aPDT‐treated groups. Subsequent assessments include cytokine levels, bacterial load, and cellular infiltrate in the ear. The P. cincinnata‐treated group exhibits improved bacterial control, reduced leukocyte infiltration, and less weight loss. The aPDT group demonstrates a unique cytokine correlation profile, featuring more negative correlations among pro‐inflammatory cytokines and interleukin‐10. P. cincinnata emerges as an effective photosensitizer for aPDT in a senescent model and highlights the potential of underexplored plant‐derived photosensitizers.

The invasive pest Halyomorpha halys (Hemiptera: Pentatomidae) poses a significant threat to agriculture and requires control methods beyond chemical pesticides. This study investigates RNA interference (RNAi) as a targeted gene silencing approach to manage H. halys populations. However, RNAi efficacy varies between insect orders, including hemipterans, due to factors such as the rapid degradation of double‐stranded RNA (dsRNA) by a DNA/RNA non‐specific nuclease (HhNSE) present in the saliva of H. halys. Notably, this study proves that double‐stranded DNA (dsDNA) can stabilise dsRNA in saliva, probably by competitively inhibiting HhNSE, which is highly expressed in salivary glands. In vivo tests targeting the clathrin heavy chain gene (HhCHC) demonstrate that a mixture of dsRNA‐CHC and dsDNA result in enhanced gene silencing when fed to H. halys, compared to dsRNA alone. While dsRNA‐CHC injection causes almost complete mortality, the dsDNA formulation do not significantly increase mortality when fed together with dsRNA‐CHC. These findings highlight the need to further investigate factors beyond nucleases such as dsRNA uptake and release mechanisms in the insect gut. Nevertheless, this study provides promising insights for improving RNAi delivery in H. halys, and perhaps other pests with such nucleases, in support of sustainable pest management solutions.

Adipose mesenchymal stem cell‐derived exosomes and the PDE4 inhibitor roflumilast (ROF) are investigated as potential treatments for chronic kidney disease (CKD). The exosomes are extracted and analyzed using electron microscopy and flow cytometry, then employed with ROF for in vivo implantation in a CKD animal model. Animals aredivided into seven groups. Group (I) Control; (II) exosomes; (III) ROF; (IV) Adriamycin (ADR); (V) ADR + exosomes, (VI) ADR + ROF, and (VII) ADR + Exosomes+ ROF. Biochemical serum indicators (creatinine, BUN), antioxidant status (GSH, MDA), and the mRNA expressions of TGF‐β1, Smad3, IL‐6, BAX, Wnt‐7, FN, and miRNA145‐5p are determined using qRT‐PCR. Histology assessment using H&E staining, ultrastructural observation using TEM, and protein expression in kidney tissue (FN1 and BAX) are assessed. The isolated exosomes showed cup‐shaped morphologyand expressed CD81, CD9, and CD63. Exosomes and ROF increased glutathione (GSH) levels while decreasing malondialdehyde (MDA) levels. Further, ROF and exosomes treatment lowered the expression of the apoptotic indicators BAX, the fibrotic markers TGFβ1, Smad3, Wnt7a, and FN1, and the inflammatory marker IL6, and increased the expression of miRNA‐145. Moreover, ROF and exosomes improved histological and ultrastructural examination. In conclusion, exosomes and ROF can protect against CKD by reducing apoptosis and fibrosis.

Spheroids are being widely studied as potential building blocks for complex organ engineering, tools for drug screening and cancer study. However, formation time has become the bottleneck of applications due to the need for large‐scale high‐quality spheroids production. Formation time is often dominated by ECM construction and not cell aggregation. Therefore, this study focuses on the influence of ultrasound detachment replacing conventional enzyme detachment on spheroid formation processes. Thanks to cell surface protein preservation in ultrasound detachment, cell aggregation time is reduced while decreasing the formation variabilities. Moreover, it is confirmed that cells are intrinsically more capable of aggregating through enzyme‐free detachment. On top of that, transplantations into rats showed equally successful engraftment properties for enzyme‐free detached cells. Finally, the impact on the real co‐cultured spheroid application was shown to be beneficial through more localized cell groups inside of the spheroids, possibly improving therapeutic effects and vascularization. Through this study, it is proved that ultrasound detachment can replace enzyme detachment without degrading the final spheroid properties but reducing the formation time, and variability and improving robustness and cell distribution. This opens up a new range of applications for better and faster spheroid formation in numerous bioengineering applications.

Cancer is one of the most pervasive and severe global diseases that cause millions of death annually. Numerous bacterial strains are found to play fundamental roles in tumor formation, growth, and metastasis. On the other hand, specific bacterial strains are discovered to induce beneficial changes to restrict tumoral growth and progression or alter the tumor microenvironment. Studies have also suggested bacteria are potential microorganisms that transfer synthetic genes or anti-tumor drugs. A particularly interesting area of study is bacterial communication, known as quorum sensing (QS), in which signal peptides adjust bacterial pathogenic traits such as virulence factor, drug resistance, and biofilm after a threshold volume of signals is reached. QS signals raised a propitious future perspective against diseases and cancer. Future comprehension of the QS system can lead to novel bacterial-based therapeutic procedures with the minimum healthy cell toxicity and higher target specificity rather than long-established methods. This review aims to highlight significant research and advancements in the field of QS to combat cancer and find more non-toxic and less-invasive treatments.

Infections caused by Enterovirus like rhinoviruses, coxsackieviruses, and polioviruses represent a significant public health concern, for which there are no antivirals available yet. The highly conserved viral 3C protease has been the primary target for antiviral development, but competitive inhibitors targeting its active site does not meet expectations in clinical studies. Previously, an unconventional allosteric site is identified on human rhinovirus 14 (HRV14) 3C, representing novel opportunities for pan-enterovirus antivirals development. Here, in silico screening of 143,621 natural products against this allosteric site is performed and 28 candidate molecules are identified, among which dihydromyricetin (DHM) and oridonin-A1 bind to HRV14 3C and allosterically inhibit its protease activity. Moreover, DHM shows minimal cytotoxicity and potent antiviral efficacy against HRV14 infections across different cell models, with selective indexes exceeding 700. Structural analysis and mutagenesis assays further pinpoint key 3C residues essential for DHM binding. Consistent with the high conservation of these residues across Enterovirus genus, DHM broadly binds and efficiently inhibits 3C proteases from not only rhinoviruses, but also coxsackieviruses, enteroviruses and polioviruses. These findings establish DHM as a unique, broad-spectrum allosteric inhibitor of Enterovirus 3C proteases and underscore its potential as a promising candidate for the development of pan-enterovirus antivirals.