The Synergistic Effects of Corbicula fluminea and Sarcodia montagneana on Alleviating Systemic Inflammation and Osteoarthritis Progression.

Osteoarthritis (OA) is a progressive disease that causes pain, stiffness, and inflammation in the affected joints. Currently, there are no effective treatments for preventing the worst outcomes, such as synovitis or cartilage degradation. Sarcodia montagneana and Corbicula fluminea are common species found in the ocean or in freshwater areas. Their extracts are demonstrated to possess both antioxidative and anti-inflammatory functions. This study aimed to investigate the synergistic effects of the extracts of Sarcodia montagneana (SME) and Corbicula fluminea (FCE) on reducing local and systemic inflammation, as well as their efficacy in OA symptom relief. An in vitro monocytic LPS-treated THP-1 cell model and in vivo MIA-induced mouse OA model were applied, and the results showed that the combinatory usage of SME and FCE effectively suppressed IFN-γ and TNF-α production when THP-1 cells were treated with LPS. SME and FCE also significantly decreased the systemic TNF-α level and joint swelling and prevented the loss of proteoglycan in the cartilage within the joints of OA mice. The data shown here provide a potential solution for the treatment of osteoarthritis.

Transumbilical Silicone Implants Breast Augmentation (TUSBA).

Transumbilical breast augmentation with pre-filled silicone implants has been performed previously, but technical challenges remain to accommodate more implant options and dissection planes. We aimed to demonstrate the feasibility of transumbilical breast augmentation using various types of pre-filled silicone implants (TUSBA), and its applicability for subglandular, subfascial, dual-plane implantation. In the early stage, TUSBA was primarily performed using endoscope-assisted blunt dissection, and later converted to full endoscopy dissection to achieve better results. Endoscope was used to confirm the pocket and check bleeding for both groups. For endoscope-assisted group, surgical techniques were modified from conventional TUBA. In full endoscopy TUSBA, the entire dissection process was performed under endoscopic monitoring. Preliminary data of patients undergoing TUSBA from June 2016 to April 2021 were retrospectively reviewed. Breast implants with smooth, textured or nanotextured surface properties and round or anatomical shapes were used, with sizes up to 500 mL. Seventy-four patients with mean age 36.4 years (range: 21-55 years) were enrolled in this study. Follow-up ranged from 1 month to 4 years and 6 months (mean: 15.6 months). No excessive postoperative pain in breast or abdomen was reported. Surgery outcomes were aesthetically pleasing in both groups. In the endoscope-assisted group, 3 (4.6%) required major revisional procedures. No revision was required in the full endoscopy group. TUSBA with various types of silicone implants is feasible, and accommodable to all dissection planes. Full endoscopy technique is helpful in reducing the higher complication rate.

Clinical summary of pediatric acute lymphoblastic leukemia patients complicated with asparaginase-associated pancreatitis in SCCLG-ALL-2016 protocol.

Asparaginase-associated pancreatitis (AAP) is a common and fatal complication after ASNase treatment in acute lymphoblastic leukemia(ALL). Here, a total of 1063 pediatric ALL patients treated with SCCLG-ALL-2016 regimen were collected since October 2016 to June 2020, including 35 patients with AAP. The clinical characteristics of AAP and non-AAP patients were compared. In AAP patients, the possible factors that affected the recurrence of AAP were analyzed, and the possible risk factors related to ALL-relapse were discussed. The results showed that age was a risk factor (P = .017) that affect the occurrence of AAP. In AAP patients, AAP tended to develop after the second use of PEG-ASNase (25.71%). In the follow-up chemotherapy, 17 patients re-exposed to ASNase and 7 cases developed AAP again with a percentage was 41.2%. There were no special factors that related with the recurrence of AAP. This study also found no association between the occurrence of AAP and prognosis of ALL, with the 4-year incidence of ALL relapse in AAP and non-AAP patients were 15.9% v.s.11.7% (HR: 1.009, 95% CI:0.370-2.752, P = .986), and there were no special factors that related with the ALL relapse among AAP patients. Based on the above results, the occurrence of AAP is related to age and should be vigilant after the second use of PEG-ASNase after use in pediatric ALL patients. Moreover, AAP is not associated with ALL relapse, but there is a high AAP recurrence rate when re-exposure to ASNase.

A flexible liposomal polymer complex as a platform of specific and regulable immune regulation for individual cancer immunotherapy.

BACKGROUND: The applicability and therapeutic efficacy of specific personalized immunotherapy for cancer patients is limited by the genetic diversity of the host or the tumor. Side-effects such as immune-related adverse events (IRAEs) derived from the administration of immunotherapy have also been observed. Therefore, regulatory immunotherapy is required for cancer patients and should be developed. METHODS: The cationic lipo-PEG-PEI complex (LPPC) can stably and irreplaceably adsorb various proteins on its surface without covalent linkage, and the bound proteins maintain their original functions. In this study, LPPC was developed as an immunoregulatory platform for personalized immunotherapy for tumors to address the barriers related to the heterogenetic characteristics of MHC molecules or tumor associated antigens (TAAs) in the patient population. Here, the immune-suppressive and highly metastatic melanoma, B16F10 cells were used to examine the effects of this platform. Adsorption of anti-CD3 antibodies, HLA-A2/peptide, or dendritic cells' membrane proteins (MP) could flexibly provide pan-T-cell responses, specific Th1 responses, or specific Th1 and Th2 responses, depending on the host needs. Furthermore, with regulatory antibodies, the immuno-LPPC complex properly mediated immune responses by adsorbing positive or negative antibodies, such as anti-CD28 or anti-CTLA4 antibodies. RESULTS: The results clearly showed that treatment with LPPC/MP/CD28 complexes activated specific Th1 and Th2 responses, including cytokine release, CTL and prevented T-cell apoptosis. Moreover, LPPC/MP/CD28 complexes could eliminate metastatic B16F10 melanoma cells in the lung more efficiently than LPPC/MP. Interestingly, the melanoma resistance of mice treated with LPPC/MP/CD28 complexes would be reversed to susceptible after administration with LPPC/MP/CTLA4 complexes. NGS data revealed that LPPC/MP/CD28 complexes could enhance the gene expression of cytokine and chemokine pathways to strengthen immune activation than LPPC/MP, and that LPPC/MP/CTLA4 could abolish the LPPC/MP complex-mediated gene expression back to un-treatment. CONCLUSIONS: Overall, we proved a convenient and flexible immunotherapy platform for developing personalized cancer therapy.

Transdermal nanolipoplex simultaneously inhibits subcutaneous melanoma growth and suppresses systemically metastatic melanoma by activating host immunity.

Benefit for clinical melanoma treatments, the transdermal neoadjuvant therapy could reduce surgery region and increase immunotherapy efficacy. Using lipoplex (Lipo-PEG-PEI-complex, LPPC) encapsulated doxorubicin (DOX) and carrying CpG oligodeoxynucleotide; the transdermally administered nano-liposomal drug complex (LPPC-DOX-CpG) would have high cytotoxicity and immunostimulatory activity to suppress systemic metastasis of melanoma. LPPC-DOX-CpG dramatically suppressed subcutaneous melanoma growth by inducing tumor cell apoptosis and recruiting immune cells into the tumor area. Animal studies further showed that the colonization and growth of spontaneously metastatic melanoma cells in the liver and lung were suppressed by transdermal LPPC-DOX-CpG. Furthermore, NGS analysis revealed IFN-γ and NF-κB pathways were triggered to recruit and activate the antigen-presenting-cells and effecter cells, which could activate the anti-tumor responses as the major mechanism responsible for the therapeutic effect of LPPC-DOX-CpG. Finally, we have successfully proved transdermal LPPC-DOX-CpG as a promising penetrative carrier to activate systemic anti-tumor immunity against subcutaneous and metastatic tumor.

Anticancer peptide Q7 suppresses the growth and migration of human endometrial cancer by inhibiting DHCR24 expression and modulating the AKT-mediated pathway.

Endometrial cancer is one of the most common malignancy affecting women in developed countries. Resection uterus or lesion area is usually the first option for a simple and efficient therapy. Therefore, it is necessary to find a new therapeutic drug to reduce surgery areas to preserve fertility. Anticancer peptides (ACP) are bioactive amino acids with lower toxicity and higher specificity than chemical drugs. This study is to address an ACP, herein named Q7, which could downregulate 24-Dehydrocholesterol Reductase (DHCR24) to disrupt lipid rafts formation, and sequentially affect the AKT signal pathway of HEC-1-A cells to suppress their tumorigenicity such as proliferation and migration. Moreover, lipo-PEI-PEG-complex (LPPC) was used to enhance Q7 anticancer activity in vitro and efficiently show its effects on HEC-1-A cells. Furthermore, LPPC-Q7 exhibited a synergistic effect in combination with doxorubicin or paclitaxel. To summarize, Q7 was firstly proved to exhibit an anticancer effect on endometrial cancer cells and combined with LPPC efficiently improved the cytotoxicity of Q7.

High Expression of Folate Receptor Alpha (FOLR1) is Associated With Aggressive Tumor Behavior, Poor Response to Chemoradiotherapy, and Worse Survival in Rectal Cancer.

Objectives: Recently, molecular medicine targeting Folate Receptor Alpha (FOLR1), which mediates intracellular folate uptake and tumor cell proliferation, has been identified in several malignancies. However, the association between FOLR1 expression and rectal cancer remains unclear. Methods: Immunostaining of FOLR1 was performed on biopsy specimens from 172 rectal cancer patients undergoing preoperative chemoradiotherapy (CRT). FOLR1 expression was measured and divided into low (0+-2+) or high (3+-4+) level. Correlations between FOLR1 status and clinicopathologic features, tumor regression grade, disease-specific survival (DSS), local recurrence-free survival, and metastasis-free survival (MeFS) were analyzed, retrospectively. Results: High FOLR1 expression was significantly associated with advanced post-treatment tumor and nodal status (T3-4; N1-2, P = .001), vascular invasion (P = .042), perineural invasion (P = .012), and poor regression change after CRT (P = .001). In uni- and multi-variable survival analysis, FOLR1 overexpression remained a significant predictor of lower DSS (hazard ratio [HR], 2.328; 95% confidence interval [CI], 1.014-5.344; P = .046) and MeFS (HR, 2.177; 95% CI, 1.000-1.1286; P = .050). Conclusion: These results indicate that high FOLR1 status is associated with aggressive tumor behavior, poor response to CRT, and worse survival. Therefore, FOLR1 expression at initial biopsy may be useful in predicting outcomes and also be a target for the exploration of FOLR1-based therapeutic agents.

High SLC28A2 expression endows an inferior survival for rectal cancer patients managed by neoadjuvant CCRT.

For rectal cancer patients with stage T3-4 disease or positive lymph node, neoadjuvant concurrent chemoradiotherapy (CCRT) has become the standard treatment, but the clinical outcomes are still far from satisfactory. Accordingly, a more precise predictive tool such as genetic biomarkers is urgently required to optimize therapy decisions. Colorectal cancer (CRC) development has been considerably correlated with cellular metabolic process involving nucleotides, but the underlying molecular mechanisms remain unclear. In this study, we employed a transcriptome dataset comprising 46 rectal adenocarcinoma patients undergoing preoperative CCRT and focused on nucleobase-containing compound metabolic process (GO: 0055134) for data mining. We identified solute carrier family 28 member 2 (SLC28A2) as the most considerably upregulated gene among rectal cancer patients with CCRT resistance. Afterwards, there were a total of 172 rectal cancer tissue blocks procuring from our biobank, and the immunointensity of SLC28A2 was appraised utilizing immunohistochemical staining. Strong SLC28A2 immunointensity was significantly linked to female patients (p = 0.032), vascular invasion (p = 0.021), and post-CCRT tumor invasion and regional lymph node involvement (p < 0.001 and p = 0.005). Notably, patients with strong SLC28A2 immunointensity had no tumor downstaging (p < 0.001). Univariate analysis revealed that high SLC28A2 immunoexpression was considerably unfavorably linked to all three endpoints: local recurrence-free survival (LRFS), metastasis-free survival (MeFS), and disease-specific survival (DSS) (all p ≤ 0.0333). Moreover, both high SLC28A2 immunoexpression and low tumor regression grade were independently unfavorable prognostic factors for all three endpoints (all p ≤ 0.013) in the multivariate analysis. Utilizing function prediction analysis, SLC28A2 upregulation was more likely to be linked with stem cell homeostasis in rectal cancer. In brief, we demonstrated that high SLC28A2 immunoexpression is substantially linked to an advanced stage, poor response to CCRT, and worse patient survival. Consequently, SLC28A2 expression can be a valuable predictive and prognostic marker for rectal cancer patients and be an encouraging therapeutic target for those with CCRT resistance.

7,8-Dihydroxyflavone accelerates recovery of Brown-Sequard syndrome in adult female rats with spinal cord lateral hemisection.

BACKGROUND: 7,8-Dihydroxyflavone (DHF) mimicks the physiological action of brain-derived neurotrophic factor (BDNF). Since local BDNF delivery to the injured spinal cord enhanced diaphragmatic respiratory function, we aimed to ascertain whether DHF might have similar beneficial effects after Brown-Sequard Syndrome in a rat model of spinal cord lateral hemisection (HX) at the 9th thoracic (T9) vertebral level. METHODS: Three sets of adult female rats were included: sham+vehicle group, T9HX+vehicle group and T9HX+DHF group. On the day of surgery, HX+DHF group received DHF (5 mg/kg) while HX+vehicle group received vehicle. Neurobehavioral function, morphology of motor neurons innervating the tibialis anterior muscle and the transmission in descending motor pathways were evaluated. RESULTS: Adult female rats received T9 HX had paralysis and loss of proprioception on the same side as the injury and loss of pain and temperature on the opposite side. We found that, in this model of Brown-Sequard syndrome, reduced cord dendritic arbor complexity, reduced cord motoneuron numbers, enlarged cord lesion volumes, reduced motor evoked potentials, and cord astrogliosis and microgliosis were noted after T9HX. All of the above-mentioned disorders showed recovery by Day 28 after surgery. Therapy with DHF significantly accelerated the electrophysiological, histological and functional recovery in these T9HX animals. CONCLUSIONS: Our data provide a biological basis for DHF as a neurotherapeutic agent to improve recovery after a Brown-Sequard syndrome. Such an effect may be mediated by synaptic plasticity and glia-mediated inflammation in the spared lumbar motoneuron pools to a T9HX.

The impact of a multispecialty operative team on colorectal cancer surgery: A retrospective study from a would-be medical center in Taiwan.

Some studies showed that when distant metastasis or locally advanced tumors were observed, the participation of 2 or more operating surgeons (combined surgery) in the operation could improve the prognosis of patients. The multispecialty operative team would perform combined surgery in colon cancer patients with some complications since 2015. The goal of this study is to confirm performing combined surgery would improve the outcomes of colon cancer patients. A retrospective observational study was conducted, which involved all colon cancer patients between November 2015 and December 2019 at one would-be medical center. Patients were divided into 3 cohorts: those with complicated cases and had combined surgery (C_2S), those with complicated cases and had surgery performed by a single surgeon (C_1S), and those with uncomplicated cases and had surgery performed by a single surgeon (NC_1S). Overall survival and disease-free survival were compared among the 3 groups. A total of 296 colon cancer patients during the study period. Among them, 35 were C_2S, 87 were C_1S, and 174 were NC_1S. Patients in the NC_1S group had significantly higher 12-, 24-, and 36-month OS rates compared to those in the C_1S group (P < .01). In contrast, there was no significant difference in overall survival among patients in the NC_1S and C_2S group (P =.15). The quality of surgery must be impact the prognosis, especially in the individual who was complicated case, the survival in patients who had surgery performed by multispecialty operative team would be improved.

An Observational Study of Trifluridine/Tipiracil-Containing Regimen Versus Regorafenib-Containing Regimen in Patients With Metastatic Colorectal Cancer.

Background: There are no randomized control trials comparing the efficacy of trifluridine/tipiracil and regorafenib in patients with metastatic colorectal cancer (mCRC). Herein, we conducted an observational study to compare the oncologic outcomes of trifluridine/tipiracil-containing regimen (TAS-102) and regorafenib-containing regimen (REG) in patients with mCRC. Material and method: Patients who were diagnosed to have mCRC in 2015 to 2021 and treated with TAS-102-containing regimen or REG-containing regimen were recruited. Monotherapy or combination therapy were all allowed in this study. Oncologic outcomes were presented with progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and disease control rate (DCR). Results: A total of 125 patients were enrolled into our study, accounting for 50 patients with TAS-102 and 75 patients with REG. Of these patients, 64% were treated with TAS-102 or REG monotherapy, while the remaining were treated with TAS-102 combination or REG combination. In general, the median PFS and OS were 3.7 versus 2.0 months (P = 0.006) and 9.2 versus 6.8 months (P = 0.048) in TAS-102 and REG, respectively. The ORR and DCR were 44% versus 20% (P < 0.001) and 72% versus 43% (P < 0.001) in TAS-102 and REG, respectively. As for treatment strategies, the survival were significantly longer in combination than in monotherapy, no matter in TAS-102 or REG group. Multivariate analysis showed TAS-102 and combination therapy were independent predictor associated with better survival. Conclusions: Our results suggested that TAS-102 had better oncologic outcomes than REG in patients with mCRC, especially in combination. Further prospective trials are warranted to confirm our results.

Human Umbilical Mesenchymal Stem Cell Xenografts Repair UV-Induced Photokeratitis in a Rat Model.

Most patients with a corneal injury are administered anti-inflammatory medications and antibiotics, but no other treatments are currently available. Thus, the corneal injury healing is unsatisfactory, affects the vision, and has a risk of blindness in severe cases. Human umbilical mesenchymal stem cells exhibit pluripotent and anti-inflammatory properties and do not cause immunological rejection in the host. Rats were irradiated with type B ultraviolet (UVB) light to generate a stable animal model of photokeratitis. After irradiation-induced photokeratitis, human umbilical mesenchymal stem cells were implanted into the subconjunctival space of the lateral sclera, and the changes in the corneal pathology were evaluated. Three weeks after implantation, many mesenchymal stem cells were visible in the subconjunctival space. These mesenchymal stem cells effectively reduced the extent of injury to the adjacent corneal tissue. They accelerated the epithelial layer repair, reduced the inflammatory response and neovascularization, and improved the disorganization of collagen and fibronectin in the corneal stroma caused by the injury. In conclusion, xenografted human umbilical mesenchymal stem cells can survive in rat eye tissues for a long time, effectively support the structural integrity of injured corneal tissues, restore corneal permeability, and reduce abnormal neovascularization. This study provides a new approach to the treatment of photokeratitis.

The Lysosome in Malignant Melanoma: Biology, Function and Therapeutic Applications.

Lysosomes are membrane-bound vesicles that play roles in the degradation and recycling of cellular waste and homeostasis maintenance within cells. False alterations of lysosomal functions can lead to broad detrimental effects and cause various diseases, including cancers. Cancer cells that are rapidly proliferative and invasive are highly dependent on effective lysosomal function. Malignant melanoma is the most lethal form of skin cancer, with high metastasis characteristics, drug resistance, and aggressiveness. It is critical to understand the role of lysosomes in melanoma pathogenesis in order to improve the outcomes of melanoma patients. In this mini-review, we compile our current knowledge of lysosomes' role in tumorigenesis, progression, therapy resistance, and the current treatment strategies related to lysosomes in melanoma.

The Effects of Freshwater Clam (Corbicula fluminea) Extract on Serum Tumor Necrosis Factor-Alpha (TNF-α) in Prediabetic Patients in Taiwan.

Freshwater clam extract (FCE) is a functional food that regulates the immune system and has been demonstrated in numerous studies to display desirable anti-tumor necrosis factor-alpha (TNF-α) responses. In addition, excess TNF-α production is positively associated with type 2 diabetes. However, few longitudinal clinical studies evaluating the efficiency and toxicity of FCE are available. This article reports that patients with prediabetes who received FCE had a desirable outcome of a reduction in serum TNF-α for a long period. This was a double-blind, randomized, parallel clinical trial conducted using FCE intervention and placebo groups, and 36 patients with prediabetes were enrolled. Two grams of FCE or placebo was consumed daily for 180 consecutive days. The serum of the participants was collected at four time points (0M: before the intervention; 3M: after 3 months of intervention; 6M: after 6 months of intervention; 12M: 6 months after cessation of intervention at 6M). A serum TNF-α concentration higher than 4.05 pg/mL was defined as a cut-off value. FCE reduced serum TNF-α in all participants at 6M and 12M. Moreover, FCE significantly suppressed serum TNF-α concentrations at 6M and 12M and inhibited TNF-α release with time series in subjects with elevated TNF-α values. FCE intervention effectively reduced serum TNF-α and persistently sustained the effects for half a year in patients with prediabetes. Gas chromatography-mass spectrometry (GS-MS) analysis revealed that the major components of FCE were phytosterols and fatty acids, which exerted anti-inflammatory and anti-TNF-α abilities. Hence, FCE has the potential to be developed as a natural treatment for prediabetic patients in Taiwan.

Surfactin induces ER stress-mediated apoptosis via IRE1-ASK1-JNK signaling in human osteosarcoma.

Osteosarcoma, one of primary bone tumor in children and young adults, has poor prognosis and drug resistances to chemotherapy. In order to reinforce the conventional therapies and antagonize the osteosarcoma in patients, a novel strategy is required for developing a new treatment. In this study, surfactin, a natural product from Bacillus subtilis, showed the efficiency of cell death in osteosarcoma, but not in normal cells. Surfactin triggers ER stress mechanism by promoting the aberrant Ca2+ release from ER lumen and ER-signaling to mitochondrial dysfunction following caspases activation mediating cell apoptosis. Surfactin-induced ER stress not only upregulated of glucose-regulated protein 78/94 and IRE1-ASK1-JNK pathway but also leading to calpains and Bcl-2 proteins family involving the release of cytochrome c. The releases into cytosol trigger the cleavage of caspase-9 and caspase-3 to induce cell apoptosis. In this study, surfactin demonstrated the potential functions to trigger the ER stress, ER stress-associated IRE1-ASK1-JNK signaling pathway, mitochondrial dysfunction, and caspase activations leading to programmed cell apoptosis. Importantly, implicating the signaling pathway that regulates the connection between ER stress and mitochondrial dysfunction causing apoptosis associated with surfactin. These results indicated a potential application of surfactin strengthen current conventional therapies.

Impact on inadequate lymph node harvest on survival in T4N0 colorectal cancer: A would-be medical center experience in Taiwan.

Insufficient lymph node harvest (< 12) may lead to incorrect classification of stage I and II disease. Many studies have indicated a poor prognosis with inadequate lymph node harvest in stages I to III, but few studies have demonstrated the relationship between low lymph node harvest and T4 disease. This study aimed to identify the influence of insufficient number of lymph nodes harvested on survival in T4N0 colorectal cancer. We enrolled patients with T4N0 colorectal cancer who underwent radical resection between 2010 and 2016. A total of 155 patients were divided into 2 groups; 142 patients had ≥ 12 harvested lymph nodes, and the other 13 had < 12 lymph nodes. All patients were followed up for at least 5 years. The primary outcome was the impact of the number of lymph nodes harvested on disease-free survival and overall survival, which were investigated using Kaplan-Meier survival techniques. There were no significant differences in recurrence rate, emergent or elective surgery, laparoscopic or open surgery, or chemotherapy between the 2 groups. Kaplan-Meier analyses showed no statistical differences in 5-year disease-free survival (P = .886) and 5-year overall survival (P = .832) between the groups. There were no significant differences in disease-free survival and overall survival between patients with adequate (≥ 12) and inadequate (< 12) lymph node harvest in T4N0 colorectal cancers.

Overexpression of MLPH in Rectal Cancer Patients Correlates with a Poorer Response to Preoperative Chemoradiotherapy and Reduced Patient Survival.

Data mining of a public transcriptomic rectal cancer dataset (GSE35452) from the Gene Expression Omnibus, National Center for Biotechnology Information identified the melanophilin (MLPH) gene as the most significant intracellular protein transport-related gene (GO:0006886) associated with a poor response to preoperative chemoradiation. An MLPH immunostain was performed on biopsy specimens from 172 rectal cancer patients receiving preoperative chemoradiation; samples were divided into high- and low-expression groups by H-scores. Subsequently, the correlations between MLPH expression and clinicopathologic features, tumor regression grade, disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS) were analyzed. MLPH expression was significantly associated with CEA level (p = 0.001), pre-treatment tumor status (p = 0.022), post-treatment tumor status (p < 0.001), post-treatment nodal status (p < 0.001), vascular invasion (p = 0.028), and tumor regression grade (p < 0.001). After uni- and multi-variable analysis of five-year survival, MLPH expression was still associated with lower DSS (hazard ratio (HR), 10.110; 95% confidence interval (CI), 2.178-46.920; p = 0.003) and MeFS (HR, 5.621; 95% CI, 1.762-17.931; p = 0.004). In conclusion, identifying MLPH expression could help to predict the response to chemoradiation and survival, and aid in personal therapeutic modification.

Protective Effects of Fucoxanthin Dampen Pathogen-Associated Molecular Pattern (PAMP) Lipopolysaccharide-Induced Inflammatory Action and Elevated Intraocular Pressure by Activating Nrf2 Signaling and Generating Reactive Oxygen Species.

Inflammation and oxidative stress are closely related processes in the pathogenesis of various ocular diseases. Uveitis is a disorder of the uvea and ocular tissues that causes extreme pain, decreases visual acuity, and can eventually lead to blindness. The pharmacological functions of fucoxanthin, isolated from brown algae, induce a variety of therapeutic effects such as oxidative stress reduction and repression of inflammation reactions. However, the specific anti-inflammatory effects of fucoxanthin on pathogen-associated molecular pattern (PAMP) lipopolysaccharide-induced uveitis have yet to be extensively described. Therefore, the aim of present study was to investigate the anti-inflammatory effects of fucoxanthin on uveitis in rats. The results showed that fucoxanthin effectively enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in ocular tissues. Furthermore, fucoxanthin significantly increased the ocular activities of superoxide dismutase and decreased the levels of malondialdehyde stimulated by PAMP-induced uveitis. Ocular hypertension and the levels of inflammatory cells and proinflammatory cytokine tumor necrosis factor-alpha in the aqueous humor were alleviated with fucoxanthin treatment. Consequently, compared to the observed effects in lipopolysaccharide groups, fucoxanthin treatment significantly preserved iris sphincter innervation and pupillary function. Additionally, PAMP-induced corneal endothelial disruption was significantly inhibited by fucoxanthin treatment. Overall, these findings suggest that fucoxanthin may protect against inflammation from PAMP-induced uveitis by promoting the Nrf2 pathway and inhibiting oxidative stress.

Enhancement of cytotoxicity and induction of apoptosis by cationic nano-liposome formulation of n-butylidenephthalide in breast cancer cells.

Breast cancer is the second most common malignancy in women. Current clinical therapy for breast cancer has many disadvantages, including metastasis, recurrence, and poor quality of life. Furthermore, it is necessary to find a new therapeutic drug for breast cancer patients to meet clinical demand. n-Butylidenephthalide (BP) is a natural and hydrophobic compound that can inhibit several tumors. However, BP is unstable in aqueous or protein-rich environments, which reduces the activity of BP. Therefore, we used an LPPC (Lipo-PEG-PEI complex) that can encapsulate both hydrophobic and hydrophilic compounds to improve the limitation of BP. The purpose of this study is to investigate the anti-tumor mechanisms of BP and BP/LPPC and further test the efficacy of BP encapsulated by LPPC on SK-BR-3 cells. BP inhibited breast cancer cell growth, and LPPC encapsulation (BP/LPPC complex) enhanced the cytotoxicity on breast cancer by stabilizing the BP activity and offering endocytic pathways. Additionally, BP and LPPC-encapsulated BP induced cell cycle arrest at the G0/G1 phase and might trigger both extrinsic as well as intrinsic cell apoptosis pathway, resulting in cell death. Moreover, the BP/LPPC complex had a synergistic effect with doxorubicin of enhancing the inhibitory effect on breast cancer cells. Consequently, LPPC-encapsulated BP could improve the anti-cancer effects on breast cancer in vitro. In conclusion, BP exhibited an anti-cancer effect on breast cancer cells, and LPPC encapsulation efficiently improved the cytotoxicity of BP via an acceleration of entrapment efficiency to induce cell cycle block and apoptosis. Furthermore, BP/LPPC exhibited a synergistic effect in combination with doxorubicin.