Pre-treatment of rapamycin transformed M2 microglia alleviates traumatic cervical spinal cord injury via AIM2 signaling pathway in vitro and in vivo.

Background: Traumatic spinal cord injury (SCI) is still devastating. It was suggested that the inhibition of mTOR may alleviate neuronal inflammatory injury but its underlying mechanism remained to be elucidated. AIM2 (absent in melanoma 2) recruits ASC (apoptosis-associated speck-like protein containing a CARD) and caspase-1 to form the AIM2 inflammasome, activate caspase-1, and elicit inflammatory responses.

Blood Pressure Variability Associates with Six-Month Outcomes in Acute Cervical Spinal Cord Injury: An Analysis of 105 Patients.

Objective: Blood pressure variability (BPV) has been shown to correlate with poor outcomes in patients with intracerebral hemorrhage (ICH) and traumatic brain injury. However, this association has not been elucidated in patients with traumatic cervical spinal cord injury (cSCI). We hypothesized that 24-hour BPV from time of admission is associated with worse outcomes in patients with cSCI.

Realistic long-term dysphagia rates after anterior cervical discectomy with fusion: is there a correlation with postoperative sagittal alignment and lordosis at a minimum 2-year follow-up?

Objective: Postoperative dysphagia after anterior cervical discectomy and fusion (ACDF) has many contributing factors, and long-term data are sparse. The authors evaluated dysphagia after ACDF based on levels fused and cervical sagittal parameters.

Methods: Patients who underwent ACDF between 2009 and 2018 at the University of California, San Francisco (UCSF), were retrospectively studied.

p53 Inhibition Protects against Neuronal Ischemia/Reperfusion Injury by the p53/PRAS40/mTOR Pathway.

The underlying mechanisms of cerebral ischemia/reperfusion (I/R) injury are unclear. Within this study, we aimed to explore whether p53 inhibition exerts protective effects via the p53/PRAS40/mTOR pathway after stroke and its potential mechanism. Both an in vitro oxygen-glucose deprivation (OGD) model with a primary neuronal culture and in vivo stroke models (dMCAO or MCAO) were used.

Does transforaminal lumbar interbody fusion induce lordosis or kyphosis? Radiographic evaluation with a minimum 2-year follow-up.

Objective: Conflicting reports exist about whether transforaminal lumbar interbody fusion (TLIF) induces lordosis or kyphosis, ranging from decreasing lordosis by 3.71° to increasing it by 18.8°.

The Effect of Anterior Cervical Discectomy and Fusion on Cervical Sagittal Vertical Axis and Lordosis with Minimum 2-Year Follow-Up.

Background: Anterior cervical discectomy and fusion (ACDF) can induce lordosis and improve cervical sagittal vertical axis (SVA), but multilevel ACDF may inadvertently increase cervical SVA because of insufficient lordosis induction.

Methods: Patients who underwent 1-, 2-, or ≥3-level ACDF in the subaxial spine with minimum 2-year follow up were retrospectively studied. C2-C7 Cobb angle (lordosis), cervical SVA, and T1 slope were measured preoperatively, immediately postoperatively, and at last follow-up.

Expression of TNF‑α and IL‑β can be suppressed via the PPAR‑γ/mTOR signaling pathway in BV‑2 microglia: A potential anti‑inflammation mechanism.

Currently, microglia are considered as crucial factors in suppressing inflammatory reactions, but the specific molecular mechanism remains unknown. To elucidate whether peroxisome proliferator‑activated receptor‑γ (PPAR‑γ) can inhibit neuroinflammatory cytokine expression via the mTOR signal pathway, the BV‑2 cell line was incubated with lipopolysaccharide (10 mM/ml) to induce an inflammatory injury. PPAR‑γ was activated by rosiglitazone, and was inhibited by GW9662.

Role of P53-Senescence Induction in Suppression of LNCaP Prostate Cancer Growth by Cardiotonic Compound Bufalin.

Bufalin is a major cardiotonic compound in the traditional Chinese medicine, Chansu, prepared from toad skin secretions. Cell culture studies have suggested an anticancer potential involving multiple cellular processes, including differentiation, apoptosis, senescence, and angiogenesis. In prostate cancer cell models, P53-dependent and independent caspase-mediated apoptosis and androgen receptor (AR) antagonism have been described for bufalin at micromolar concentrations.

Involvement of ROS-p38-H2AX axis in novel curcumin analogues-induced apoptosis in breast cancer cells.

Curcumin-based structural modification for developing more effective curcumin analogues has been drawning increasing attention. As alternative approach, using LC/MS guided purification, we previously obtained a series of novel natural terpene-conjugated curcuminoids from turmeric, and some of them exhibited even more potent anti-cancer activity against multiple types of cancer cells than curcumin. The purpose of this follow-up study was designed to decipher the mechanisms involved in anti-cancer activity of these novel curcumin analogues.

Involvement of autophagy induction in penta-1,2,3,4,6-O-galloyl-β-D-glucose-induced senescence-like growth arrest in human cancer cells.

Growing evidence has demonstrated that autophagy plays important and paradoxical roles in carcinogenesis, while senescence is considered to be a crucial tumor-suppressor mechanism in cancer prevention and treatment. In the present study we demonstrated that both autophagy and senescence were induced in response to penta-1,2,3,4,6-O-galloyl-β-D-glucose (PGG), a chemopreventive polyphonolic compound, in multiple types of cancer cells. Analysis of these 2 events over the experimental time course indicated that autophagy and senescence occurred in parallel early in the process and dissociated later.

Density functional theory calculations in stereochemical determination of terpecurcumins J-W, cytotoxic terpene-conjugated curcuminoids from Curcuma longa L.

Fourteen novel terpene-conjugated curcuminoids, terpecurcumins J-W (1-14), have been isolated from the rhizomes of Curcuma longa L. Among them, terpecurcumins J-Q and V represent four unprecedented skeletons featuring an unusual core of hydrobenzannulated[6,6]-spiroketal (1 and 2), bicyclo[2.2.

Involvement of unfolded protein response, p53 and Akt in modulation of porcine reproductive and respiratory syndrome virus-mediated JNK activation.

Our previous study has shown that activation of JNK plays a critical role in Porcine reproductive and respiratory syndrome virus (PRRSV)-mediated apoptosis. In this follow-up study, we further investigated the mechanisms involved in modulation of PRRSV-mediated JNK activation and apoptosis. We found that unfolded protein response (UPR) was induced in response to PRRSV infection which in turn triggered JNK activation and apoptosis.

Autophagy-dependent EIF2AK3 activation compromises ursolic acid-induced apoptosis through upregulation of MCL1 in MCF-7 human breast cancer cells.

Ursolic acid (UA) is a pentacyclic triterpenoid with promising cancer chemopreventive properties. A better understanding of the mechanisms underlying anticancer activity of UA is needed for further development as a clinically useful chemopreventive agent. Here, we found that both endoplasmic reticulum (ER) stress and autophagy were induced by UA in MCF-7 human breast cancer cells.

Terpecurcumins A-I from the rhizomes of Curcuma longa: absolute configuration and cytotoxic activity.

Terpecurcumins A-I (1-9), together with three known analogues (10-12), were isolated from the rhizomes of Curcuma longa (turmeric). They were derived from the hybridization of curcuminoids and bisabolanes. The structures and absolute configurations of 1-9 were elucidated on the basis of extensive spectroscopic data analysis, including NMR and electronic circular dichroism spectra.

Pseudolaric acid B induces caspase-dependent apoptosis and autophagic cell death in prostate cancer cells.

Previous studies have shown that Pseudolaric acid B (PAB), a medicinal plant-derived terpenoid, is a promising chemopreventive or therapeutic agent against various types of cancer. However, less is known regarding its activity against prostate cancer. The objective of the current study is designed to determine the anti-prostate cancer effects of PAB.

Enhanced apoptotic effects by the combination of curcumin and methylseleninic acid: potential role of Mcl-1 and FAK.

Curcumin and methylseleninic acid (MSeA) are well-documented dietary chemopreventive agents. Apoptosis appears to be a major mechanism for both agents to exert anti-cancer activity. The purpose of the present study was designed to determine whether the apoptotic effect on human cancer cells can be enhanced by combining curcumin with MSeA.

Activation of c-Jun NH(2)-terminal kinase is required for porcine reproductive and respiratory syndrome virus-induced apoptosis but not for virus replication.

Apoptosis of host cells plays a critical role in pathogenesis of virus infection. MAPK kinases especially stress-activated protein kinases c-Jun NH(2)-terminal kinase (SAPK/JNK) and p38 are often involved in virus-mediated apoptosis. It has been shown that porcine reproductive and respiratory syndrome virus (PRRSV) infection resulted in apoptosis of the host cells both in vitro and in vivo.

Methylseleninic acid potentiates multiple types of cancer cells to ABT-737-induced apoptosis by targeting Mcl-1 and Bad.

ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins, holds great promise to complement current cancer therapies. However many types of solid cancer cells are resistant to ABT-737. One practical approach to improve its therapeutic efficacy is to combine with the agents that can overcome such resistance to restore the sensitivity.

p53 activation inhibits ochratoxin A-induced apoptosis in monkey and human kidney epithelial cells via suppression of JNK activation.

Ochratoxin A (OTA), one of the major food-borne mycotoxins, induces apoptosis in various types of cells. Induction of apoptosis is suggested to be one of the major cellular mechanisms behind OTA-induced diverse toxic effects. However, the molecular mechanisms involved, especially the role of p53 in OTA-induced apoptosis have not been clearly elucidated.

Biotransformation of bufadienolides by cell suspension cultures of Saussurea involucrata.

The biotransformation of three bioactive bufadienolides, namely, bufotalin (1), telocinobufagin (2), and gamabufotalin (3) by cell suspension cultures of Saussurea involucrata yielded 11 products. Bufotalin yielded 3-epi-bufotalin (1a), 3-epi-desacetylbufotalin (1b), 3-epi-bufotalin 3-O-β-D-glucoside (1c), 1β-hydroxybufotalin (1d), and 5β-hydroxybufotalin (1e); telocinobufagin yielded 3-dehydroscillarenin (2a), 3-dehydrobufalin (2b), and 3-epi-telocinobufagin (2c); and gamabufotalin yielded 3-epi-gamabufotalin (3a), 3-dehydrogamabufotalin (3b), and 3-dehydro-Δ¹-gamabufotalin (3c), respectively. Among these 11 products, 1a, 1b, 1c, 1d, 3a and 3c are previously unreported.

Penta-1,2,3,4,6-O-galloyl-beta-D-glucose induces senescence-like terminal S-phase arrest in human hepatoma and breast cancer cells.

Senescence is a permanent growth arrest and has been implicated as an efficient anti-carcinogenesis mechanism. The purpose of this study was designed to test the hypothesis that penta-1,2,3,4,6-O-galloyl-beta-D-glucose (PGG), a naturally occurring polyphonolic gallotannin compound, might induce this type of permanent growth arrest in cancer cells. Our results show, for the first time, that PGG-induced senescence-like S-phase arrest in HepG2, Huh-7 human hepatoma cells, and SKBr3 human breast cancer cells at sublethal doses, judged by cellular morphological changes, increased senescence-associated β-galactosidase (SA-β-gal) activity, together with loss of proliferative capacity after being released from the treatment.

Bufadienolide compounds sensitize human breast cancer cells to TRAIL-induced apoptosis via inhibition of STAT3/Mcl-1 pathway.

The death receptor ligand TRAIL is considered a promising candidate for cancer therapy because of its preferential toxicity to malignant cells. However its efficacy has been challenged by a number of resistance mechanisms. Therefore, agents that can overcome the resistance to enhance therapeutic efficacy of TRAIL are needed.