Nan-Fu Chen

Background and Clinical Significance: We report a rare case of a 66-year-old male with malignant non-germinal center-type large B-cell lymphoma involving the thoracic epidural, cauda equina, and filum terminal simultaneously. Case Presentation: The patient complained of back pain, rapid progressive numbness, and motor palsy in both legs in one month. Neurological examination revealed grade 2 muscle power in both lower limbs, hypesthesia below the T8 dermatome, and bladder and bowel dysfunctions. Magnetic resonance imaging (MRI) with contrast showed a well-defined extradural lesion extending from the T7 to T9 level, with severe spinal cord compression. Additionally, it revealed enlargement of the cauda equina occupying the extradural space from the L1-S1 level. The lesion appeared isointense on T1, mildly hyperintense on T2-weighted images, and exhibited homogeneous enhancement on post-contrast images. To relieve the patient’s spinal cord compression as soon as possible and allow the patient to recover quickly after surgery, we performed unilateral biportal endoscopy (UBE) to completely remove the T7-9 epidural lesion. The immunohistochemical assessment confirmed a histological diagnosis of diffuse large B-cell lymphoma, a non-germinal center type. The patient received radiotherapy to the thoracic and lumbosacral areas (50 Gy) and chemotherapy with six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) after surgery. Follow-up positron emission tomography (PET) scan and MRI performed 4 months after surgery revealed complete remission of the lesion. The patient was able to walk using a walker after therapy. Conclusions: UBE is a favorable option for selected patients requiring immediate chemotherapy or radiotherapy owing to its reduced tissue trauma compared to traditional open surgery.

Background and Clinical Significance: We report a rare case of a 66-year-old male with malignant non-germinal center-type large B-cell lymphoma involving the thoracic epidural, cauda equina, and filum terminale simultaneously. Case Presentation: The patient complained of back pain, rapid progressive numbness, and motor palsy in both legs in one month. Neurological examination revealed grade 2 muscle power in both lower limbs, hypesthesia below the T8 dermatome, and bladder and bowel dysfunctions. Magnetic resonance imaging (MRI) with contrast showed a well-defined extradural lesion extending from the T7 to T9 level, with severe spinal cord compression. Additionally, it revealed enlargement of the cauda equina occupy-ing the extradural space from the L1‑S1 level. The lesion appeared isointense on T1, mildly hyperintense on T2-weighted images, and exhibited homogeneous enhance-ment on post-contrast images. To relieve the patient’s spinal cord compression as soon as possible and allow the patient to recover quickly after surgery, we performed uni-lateral biportal endoscopy (UBE) to completely remove the T7-9 epidural lesion. The immunohistochemical assessment confirmed a histological diagnosis of diffuse large B-cell lymphoma, a non-germinal center type. The patient received radiotherapy to the thoracic and lumbosacral areas (50 Gy) and chemotherapy with six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) after sur-gery. Follow-up positron emission tomography (PET) scan and MRI performed 4 months after surgery revealed complete remission of the lesion. The patient was able to walk using a walker after therapy. Conclusions: UBE is a favorable option for selected patients requiring immediate chemotherapy or radiotherapy owing to its reduced tissue trauma compared to traditional open surgery.

Introduction: Neuropathic pain (NP) affects countless people worldwide; however, few effective treatments are currently available. Histone deacetylases (HDACs) participate in epigenetic modifications in neuropathy-induced nociceptive sensitization. Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that can inhibit NP. The present study aimed to examine the role of spinal HDAC and its isoforms in neuropathy. Methods: Male Wistar Rat with chronic constriction injury (CCI)-induced peripheral neuropathy and HDAC inhibitor, panobinostat, was administrated intrathecally. We performed quantitative real-time polymerase chain reaction (RT-qPCR), western blot, and immunohistochemical analysis of lumbar spinal cord dorsal horn and nociceptive behaviors (thermal hyperalgesia and mechanical allodynia) measurements. Results: Herein, RT-qPCR analysis revealed that spinal hdac3, hdac4, and hdac6 were upregulated in CCI rats. Western blotting and immunofluorescence staining further confirmed that HDAC3, HDAC4, and HDAC6 were significantly upregulated, whereas GABA and its synthesis key enzyme glutamic acid decarboxylase (GAD) 65 were dramatically downregulated. Intrathecal panobinostat attenuated nociceptive behavior and restored the downregulated spinal GAD65 and GABA expression in CCI rats. Conclusions: HDAC upregulation might induce nociception through GAD65 and GABA inhibition in CCI-induced neuropathy. These findings strongly suggest that HDACs negatively regulate inhibitory neurotransmitters, constituting a potential therapeutic strategy for an epigenetic approach to manage NP.

The high mortality rate of glioblastoma multiforme (GBM), a lethal primary brain tumor, is attributable to postsurgical recurrence. STAT3, an oncogenic protein, is a signal transducer and transcription activator encourages cancer cell migration and proliferation, which results in resistance to therapy. STAT3 inhibition reduces cancer metastasis and improves patient prognosis. Bt354, a small molecule STAT inhibitor, exhibits significant cytotoxic and anti‐proliferative activities against certain cancer types. Here, we demonstrated that exposure of GBM cells (U87 MG) to Bt354 had a significant, concentration‐dependent growth suppression. Bt354 also induced apoptosis and downregulated the expression of the epithelial‐mesenchymal transition genes. Therefore, this study suggests the potential of Bt354 for treating GBM owing to its ability to induce cytotoxicity.

Osteosarcoma (OS) is the most common primary malignant bone tumor that produces immature osteoid. Metastatic OS has a poor prognosis with a death rate of >70%. Manoalide is a natural sesterterpenoid isolated from marine sponges. It is a phospholipase A2 inhibitor with anti-inflammatory, analgesic, and anti-cancer properties. This study aimed to investigate the mechanism and effect of manoalide on OS cells. Our experiments showed that manoalide induced cytotoxicity in 143B and MG63 cells (human osteosarcoma). Treatment with manoalide at concentrations of 10, 20, and 40 µM for 24 and 48 h reduced MG63 cell viability to 45.13–4.40% (p < 0.01). Meanwhile, manoalide caused reactive oxygen species (ROS) overproduction and disrupted antioxidant proteins, activating the apoptotic proteins caspase-9/-3 and PARP (Poly (ADP-ribose) polymerase). Excessive levels of ROS in the mitochondria affected oxidative phosphorylation, ATP generation, and membrane potential (ΔΨ_m). Additionally, manoalide down-regulated mitochondrial fusion protein and up-regulated mitochondrial fission protein, resulting in mitochondrial fragmentation and impaired function. On the contrary, a pre-treatment with n-acetyl-l-cysteine ameliorated manoalide-induced apoptosis, ROS, and antioxidant proteins in OS cells. Overall, our findings show that manoalide induces oxidative stress, mitochondrial dysfunction, and apoptosis, causing the cell death of OS cells, showing potential as an innovative alternative treatment in human OS.

Aaptamine, a natural marine compound isolated from the sea sponge, has various biological activities, including delta-opioid agonist properties. However, the effects of aaptamine in neuropathic pain remain unclear. In the present study, we used a chronic constriction injury (CCI)-induced peripheral neuropathic rat model to explore the analgesic effects of intrathecal aaptamine administration. We also investigated cellular angiogenesis and lactate dehydrogenase A (LDHA) expression in the ipsilateral lumbar spinal cord after aaptamine administration in CCI rats by immunohistofluorescence. The results showed that aaptamine alleviates CCI-induced nociceptive sensitization, allodynia, and hyperalgesia. Moreover, aaptamine significantly downregulated CCI-induced vascular endothelial growth factor (VEGF), cluster of differentiation 31 (CD31), and LDHA expression in the spinal cord. Double immunofluorescent staining showed that the spinal VEGF and LDHA majorly expressed on astrocytes and neurons, respectively, in CCI rats and inhibited by aaptamine. Collectively, our results indicate aaptamine’s potential as an analgesic agent for neuropathic pain. Furthermore, inhibition of astrocyte-derived angiogenesis and neuronal LDHA expression might be beneficial in neuropathy.

Glioblastoma multiforme (GBM) is a cancer of largely unknown cause that leads to a 5-year survival rate of approximately 7% in the United States. Current treatment strategies are not effective, indicating a strong need for the development of novel therapies. In this study, the outcomes of sinularin, a marine-derived product, were evaluated against GBM. Our cellular studies using GBM cells revealed that sinularin induces cell death. The measured half maximal inhibitory concentrations (IC₅₀) values ranged from 30 to 6 μM at 24–72 h. Cell death was induced via the generation of ROS leading to mitochondria-mediated apoptosis. This was evidenced by annexin V/propidium iodine staining and an upregulation of cleaved forms of the pro-apoptotic proteins caspase 9, 3, and PARP, and supported by CellROX^TM Green, MitoSOX^TM Red, and CM-H₂DCFDA staining methods. In addition, we observed a downregulation of the antioxidant enzymes SOD1/2 and thioredoxin. Upon treatment with sinularin at the ~IC₅₀ concentration, mitochondrial respiration capacities were significantly reduced, as shown by measuring the oxygen consumption rates and enzymatic complexes of oxidative phosphorylation. Intriguingly, sinularin significantly inhibited indicators of angiogenesis such as vessel tube formation, cell migration, and cell mobility in human umbilical vein endothelial cells or the fusion cell line EA.Hy926. Lastly, in a transgenic zebrafish model, intersegmental vessel formation was also significantly inhibited by sinularin treatment. These findings indicate that sinularin exerts anti-brain cancer properties that include apoptosis induction but also antiangiogenesis.

Over the past few years, the concern for green chemistry and sustainable development has risen dramatically. Researchers make an effort to find solutions to difficult challenges using green chemical processes. In this study, we use oyster shells as a green chemical source to prepare calcium oxide nanoparticles (CaO-NPs). Transmission electron microscopy (TEM) results showed the CaO-NPs morphology, which was spherical in shape, 40 ± 5 nm in diameter, with uniform dispersion. We further prepared silver/polydopamine/calcium-oxide (Ag/PDA/CaO) nanocomposites as the surface-enhanced Raman scattering (SERS) substrates and evaluated their enhancement effect using the methyl parathion pesticide. The effective SERS detection limit of this method is 0.9 nM methyl parathion, which is much lower than the safety limits set by the Collaborative International Pesticides Analytical Council for insecticide in fruits. This novel green material is an excellent SERS substrate for future applications and meets the goal of green chemistry and sustainable development.