In a castrated PC-3 xenograft model, PLP (400 mg/kg/day) suppressed tumor volume growth by 91.7% and tumor weight growth by 78.0% compared with the control group, showing efficacy comparable to abiraterone/prednisone without hepatorenal toxicity...Integrative transcriptomic and multi-omics analyses revealed coordinated downregulation of phosphatidylinositol 3-kinase-protein kinase B-mechanistic target of rapamycin signaling and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Functional validation showed that overexpression of phosphoinositide-3-kinase regulatory subunit 1 rescued PLP-induced tumor suppression, whereas knockdown of PGC-1α abolished its antioxidative and antiproliferative effects, indicating that both pathways are critically involved. These findings suggest that PLP combats CRPC by simultaneously inhibiting oncogenic signaling and mitigating oxidative stress, positioning it as a promising natural therapeutic candidate for CRPC.

Circadian oscillators act as temporal gatekeepers of stem-cell function. Mapping the molecular interfaces between clock genes and developmental signaling pathways reveals new opportunities to refine regenerative therapies. Chronotherapeutic strategies, i.e. timing interventions to intrinsic circadian phases may enhance the efficacy, precision, and safety of stem-cell-based treatments.

Patch-clamp recordings revealed that zeta inhibitory peptide inhibited the amplitude of evoked excitatory postsynaptic currents (EPSCs) and the frequency of miniature EPSCs in CPTP and KIBRA overexpression groups. These results demonstrate that KIBRA in ACC neurons significantly contributes to CPTP by p-PKMζ/GluR1 and neuroinflammation, offering novel mechanistic insights. However, as the study was conducted exclusively in male animals, and studies in clinical settings have shown that the CPTP prevalence is higher among females, the findings primarily apply to males, underscoring the need for future sex-specific investigations.

Electromyography (EMG) was used to assess latency and amplitude ratios (affected/healthy side) of the frontal, orbicularis oculi, and orbicularis oris muscles...The total effective rate in the observation group was 93.1% (27/29), higher than that in the control group (82.1%, 23/28, P<0.05). Acupotomy combined with acupuncture could promote recovery of facial nerve function and shorten the duration of mastoid region pain in patients with acute peripheral facial paralysis with mastoid region pain.

P2, N=7, Terminated, M.D. Anderson Cancer Center | Trial completion date: Apr 2027 --> Mar 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Apr 2027 --> Mar 2026; <75% participation

In addition, IRX6 expression showed associations with reduced sensitivity to abiraterone, suggesting a potential link with therapeutic resistance in these tumours. Collectively, these findings highlight the context-dependent expression patterns and clinical associations of IRX genes across hormone-driven cancers. While largely correlative, this study provides a framework for future functional investigations and suggests that selected IRXs may have potential utility as biomarkers for disease stratification and treatment response in hormone-sensitive cancers.

Vasomotor pulsations may arise from amplitude modulations of respiratory (RPE) and cardiovascular (CHE) pulsations while cardiovascular fluctuations may be modulated by respiration through cardiorespiratory amplitude modulation (CREM)...While elevations in all pulsations were present within (peri)tumoral regions, AFRPE elevations extended into extra-tumoral white matter and grey matter. Thus, altered cardiorespiratory fluctuations give rise to dysfunctional vasomotor and CSF pulsations in PCNSL, predicting impaired glymphatic function.

Using patch-clamp recordings in cultured cortical neurons we found that lactate enhances NMDA receptor currents (INMDAR), increasing their amplitude and decay time constant...Lactate strengthens the interaction between CaMKII and GluN2B through redox-sensitive cysteine residues in GluN2B, facilitating synaptic localization of this complex and enhancing synaptic responses. These findings reveal a molecular pathway by which lactate, produced by astrocytes, can significantly influence neuronal activity and synaptic function, linking brain metabolism with learning and memory processes.

Overall, the results indicate that maintaining Abiraterone treatment in combination with PARPis after resistance develops provides superior therapeutic efficacy compared to PARP inhibition alone, offering a promising strategy for managing Abiraterone-resistant prostate cancer. Combining Abiraterone with PARPis enhances therapeutic efficacy and overcomes the acquired insensitivity in mCRPC with BRCA1/2 or HRR mutations. These results support continued use of PARPis with Abiraterone to improve clinical outcomes.

Scheduled exercise at ZT2 significantly increased the amplitude of Per2, Per3, and Rev-Erbα expression rhythms in tumor tissue...TNF-α acrophase was shifted in the ZT2 group, indicating a temporal immunomodulatory effect. Consistently performing exercise at the same time of day enhances tumor circadian clock genes rhythmicity, supporting chrono-exercise as a potential non-pharmacological adjuvant in cancer treatment.

This suggests a limited response amplitude within the RMP/NRF2-high context...This dynamic accounts for the relatively lower inhibition observed in the overexpression context. The combined RMP/NRF2/PD-L1 signature proposes a mechanistically informed biomarker framework and suggests the potential for rational therapeutic combinations that pair PD-1 blockade with modulation of the redox pathway in HCC.

Inflachromene, an inhibitor of the chromatin remodelers HMGB1/2, decoupled mitochondrial bioenergetics from senolytic susceptibility, yielding SASP-null/miR146a-negative senescent cancer cells that were completely resistant to ABT-263/navitoclax and A1331852 despite extensive mitochondrial reprogramming. Thus, the senolytic response is governed by a layered circuit in which mitochondrial bioenergetic heritage establishes the senolytic ceiling, TIS-acquired bioenergetic flexibility fine-tunes the amplitude of the senolytic response, and establishing a mitochondria-inflammatory SASP crosstalk is required for BH3-mediated senolysis. These results support using functional readouts that integrate mitochondrial metabolic flexibility and inflammatory SASP to predict and potentially enhance senolytic efficacy in TIS cancer cells.