Insect-derived extracts and peptides in neuroprotection.

Throughout history, various cultures have recognized the significance of insects and have integrated them into traditional medicinal practices. In addition to medicines, insects are garnering attention as a sustainable and nutritious dietary alternative. Although edible insects have long been recognized as food sources in many Asian cultures, recent scientific studies have highlighted their potential therapeutic benefits, particularly in the field of neuroprotection. This review explores insect-derived extracts and peptides, elucidating their neuroprotective potential. This review highlights the potential use of insects as a source of neuroprotective agents. Advancements in neuroprotection may find a key ally in insects as our understanding of the symbiotic relationship between insects and human health becomes more profound.

Photobiomodulation Mitigates PM2.5-Exacerbated Pathologies in a Mouse Model of Allergic Asthma.

Exposure to particulate matter (PM), especially PM2.5, is known to exacerbate asthma, posing a significant public health risk. This study investigated the asthma-reducing effects of photobiomodulation (PBM) in a mice model mimicking allergic airway inflammation exacerbated by PM2.5 exposure. The mice received sensitization with ovalbumin (OVA) and were subsequently treated with PM2.5 at a dose of 0.1 mg/kg every 3 days, for 9 times over 3 weeks during the challenge. PBM, using a 610 nm wavelength LED, was applied at 1.7 mW/cm2 to the respiratory tract via direct skin contact for 20 min daily for 19 days. Results showed that PBM significantly reduced airway hyperresponsiveness, plasma immunoglobulin E (IgE) and OVA-specific IgE, airway inflammation, T-helper type 2 cytokine, histamine and tryptase in bronchoalveolar lavage fluid (BALF), and goblet cell hyperplasia in PM2.5-exposed asthmatic mice. Moreover, PBM alleviated subepithelial fibrosis by reducing collagen deposition, airway smooth muscle mass, and expression of fibrosis-related genes. It mitigated reactive oxygen species generation, oxidative stress, endoplasmic reticulum stress, apoptotic cell death, ferroptosis, and modulated autophagic signals in the asthmatic mice exposed to PM2.5. These findings suggest that PBM could be a promising intervention for PM2.5-induced respiratory complications in patients with allergic asthma.

Albumin Leakage Level during Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Is Associated with Major Complications.

The clinical consequences of perioperative albumin extravasation accompanying major abdominal surgery remain underexplored. We retrospectively reviewed the data of patients who underwent cytoreductive surgery (CRS) and hyperthermic intraoperative peritoneal chemotherapy (HIPEC). Parameters of albumin kinetics, including serum albumin concentration decrease (∆Alb) and extravasated albumin level (Albshift), were assessed from surgery until postoperative day (POD) 3. Logistic regression analysis identified factors associated with major complications. The association of albumin kinetics with major complications was evaluated using receiver operating characteristic (ROC) curve analysis. Serum albumin levels decreased during surgery and subsequently increased. Of the 121 analyzed patients, 25 (21%) developed major complications. The ∆Alb and Albshift during surgery and on POD 3 were greater in patients who developed major complications than in those who did not (12 ± 12 vs. 6 ± 14, p = 0.032, and 127.5 (71.9) vs. 48.5 (44.9), p < 0.001, respectively). Perioperative ∆Alb and Albshift were associated with major complications. The areas under the ROC curve of Albshift during the 3 days post-surgery and Albshift on POD 3 were 0.843 and 0.910, respectively. Albshift during the 3 days post-surgery and Albshift on POD 3 were correlated with complications (p < 0.05). In conclusion, perioperative albumin loss was associated with major complications in patients undergoing CRS and HIPEC. Albshift was associated with serious complications.

Prognostic Value of the Controlling Nutritional Status (CONUT) Score in Patients Who Underwent Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Chemotherapy.

The Controlling Nutritional Status (CONUT) score is a novel nutritional index that integrates the serum albumin level, peripheral blood lymphocyte count, and total cholesterol level. This retrospective study explores its prognostic significance in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). We included 436 patients who underwent CRS-HIPEC, categorized into low (0-3) and high (4-12) CONUT score groups, and performed logistic regression analysis to predict one-year mortality and postoperative morbidity. Our findings revealed that high CONUT scores correlate with increased one-year mortality (47.1% vs. 20.3%, p < 0.001) and morbidity (39.2% vs. 18.2%, p < 0.001) compared to low CONUT scores. Multivariable regression analysis confirmed high CONUT scores as independent predictors of one-year mortality (odds ratio: 2.253, 95% CI: 1.014-5.005, p = 0.046) and postoperative morbidity (odds ratio: 2.201, 95% CI: 1.066-4.547, p = 0.033). These results underscore the CONUT score's effectiveness as an independent marker for evaluating risks associated with CRS-HIPEC, emphasizing its potential to improve risk stratification.

The formation of lamellar body-like structures may be a trigger of cetylpyridinium chloride-induced cell death and inflammatory response.

Cetylpyridinium chloride (CPC) is a quaternary ammonium compound used widely in health and personal care products. Meanwhile, due to its increasing use, its potential adverse health effects are emerging as a topic of public concern. In this study, we first administered CPC by pharyngeal aspiration to determine the survival level (the maximum concentration at which no death is observed) and then administered CPC to mice repeatedly for 28 days using the survival level as the highest concentration. CPC increased the total number of pulmonary cells secreting pro- and anti-inflammatory cytokines and chemokines. Infiltration of inflammatory cells, production of foamy alveolar macrophages, and chronic inflammatory lesions were found in the lung tissue of male and female mice exposed to the highest dose of CPC. We also investigated the toxicity mechanism using BEAS-2B cells isolated from normal human bronchial epithelium. At 6 h after exposure to CPC, the cells underwent non-apoptotic cell death, especially at concentrations greater than 2 µg/mL. The expression of the transferrin receptor was remarkably enhanced, and the expression of proteins that contribute to intracellular iron storage was inhibited. The expression of both mitochondrial SOD and catalase increased with CPC concentration, and PARP protein was cleaved, suggesting possible DNA damage. In addition, the internal structure of mitochondria was disrupted, and fusion between damaged organelles was observed in the cytoplasm. Most importantly, lamellar body-like structures and autophagosome-like vacuoles were found in CPC-treated cells, with enhanced expression of ABCA3 protein, a marker for lamellar body, and a docking score between ABCA3 protein and CPC was considered to be approximately -6.8969 kcal/mol. From these results, we propose that mitochondrial damage and iron depletion may contribute to CPC-induced non-apoptotic cell death and that pulmonary accumulation of cell debris may be closely associated with the inflammatory response. Furthermore, we hypothesize that the formation of lamellar body-like structures may be a trigger for CPC-induced cell death.

Long-Term Dietary Consumption of Grapes Affects Kidney Health in C57BL/6J Mice.

Starting at 4 weeks of age, male and female C57BL/6J mice were provided with a semi-synthetic diet for a period of one year and then continued on the semi-synthetic diet with or without grape supplementation for the duration of their lives. During the course of the study, no variation of body weights was noted between the groups. At 2.5 years of age, the body-weight-to-tissue-weight ratios did not vary for the liver, colon, muscle, prostate, or ovary. However, relative to the standard diet, the body/kidney weight ratio was significantly lower in the male and female groups with grape-supplemented diets. With the mice provided with the standard diet, the BUN/creatinine ratios were 125 and 152 for males and females, respectively, and reduced to 63.7 and 40.4, respectively, when provided with the grape diet. A histological evaluation suggested that this may be due to enhanced/improved perfusion in the kidney as a preventive/protective effect. In response to the dietary grapes, an RNA seq analysis revealed up-regulation of 21 and 109 genes with male and female mice, respectively, with a corresponding down-regulation of 108 and 65 genes. The downward movement of the FPKM values in the males (alox5, btk, fga, fpr1, hmox1, lox, ltf, lyve1, marco, mmp8, prg4, s100a8/9, serpina3n, and vsig4) and upward movement of the FPKM values in the females (camp, cd300lf, cd72, fcgr4, fgr, fpr2, htra4, il10, lilrb4b, lipg, pilra, and tlr8) suggest beneficial kidney effects. The expression of some genes related to the immunological activity was also modulated by the grape diet, mainly downward in the males and upward in the females. The reactome pathway analysis, KEGG analysis, and GSEA normalized enrichment scores illustrate that several pathways related to immune function, collagenase degradation, extracellular matrix regulation, metabolism of vitamins and cofactors, pancreatic secretion, aging, and mitochondrial function were enriched in both the males and females provided with the grape diet. Overall, these results indicate that the long-term dietary consumption of grapes contributes to renal health and resilience against fibrosis and related pathologies.

High-molecular-weight Fucoidan exerts an immune-enhancing effect in RAW 264.7 cells and cyclophosphamide-induced immunosuppression rat by altering the gut microbiome.

High-molecular-weight fucoidan (Fucoidan P), sourced from Undaria pinnatifida exhibits several health benefits, including immunomodulation. However, the mechanisms underlying the immune-enhancing effects of Fucoidan P remain unclear. Here, we investigated the immune-enhancing effects and the potential mechanisms of Fucoidan P using RAW 264.7 macrophages and cyclophosphamide (CP)-induced immunosuppression rat model. In macrophages, Fucoidan P showed dose-dependent stimulation by increasing cell proliferation, nitric oxide production, and gene expression of inducible nitric oxide synthase, cyclooxygenase-2, and proinflammatory cytokines. These effects are mediated through the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. Moreover, orally administered Fucoidan P was evaluated in immunosuppressed rats treated with CP. Fucoidan P administration increased hematological values and natural killer cell activity, and positively affected nitrite and prostaglandin E2 levels. The Fucoidan P treatment groups exhibited improved serum cytokine levels as well as splenic and intestinal cytokine mRNA expression compared to the model group. Fucoidan P also mitigated splenic damage and increased the phosphorylation of NF-κB and NF-κB inhibitor alpha (IκBα). Furthermore, Fucoidan P treatment altered the gut microbiota composition, enhancing the alpha diversity, evenness, and abundance of Bacteroidetes, which are associated with immune function. Taken together, our findings suggest that Fucoidan P exerts beneficial effects on immune function by activating NF-κB and modulating gut microbiota. These findings suggested its potential as a therapeutic agent for immune enhancement.

General toxicity and screening of reproductive and developmental toxicity following bioaccumulation of oral-dosed perfluorooctanoic acid: Loss of the Golgi apparatus.

Despite its widespread use as a stabilizer across various industries over the past several decades, the health effects of chronic exposure to PFOA are still unclear. We administered PFOA by oral gavage (0, 12.5, 50, and 200 µg/day/mouse, eight groups) to male and female mice for six months. Body weight gain decreased with dose accompanied by increased liver weight, and PFOA altered liver damage-related-blood biochemical indicators and induced pathological lesions, including hepatocellular hypertrophy, cholangiofibrosis, and centrilobular hepatocellular vacuolation. Loss of the Golgi apparatus, formation of lamellar body-like structures, and lipid accumulation were observed in the liver of PFOA-treated mice. We also cohabited five pairs of male and female mice for the last ten days of administration, dosed PFOA to dam up to 28 days after birth, and investigated effects on reproduction and development. The survival rate of pups and the sex ratio of surviving mice decreased significantly at the highest dose. PFOA tissue concentration increased with the dose in the parent mice's liver and the pups' blood and brain. Taken together, we suggest that PFOA primarily affects the liver and reproduction system and that disturbance in lipid metabolism and Golgi's structural stability may be involved in PFOA-induced toxicity.

The obesogen bisphenol A promotes adipogenesis in canine adipose-derived stem cells: Potential implication in dog obesity.

The growing number of companion dogs has contributed to a rapidly growing market for pet products, including dog toys. However, little is known about the hazardous substances released from dog toys. This study aims to examine the potential presence of obesogens, a subset of endocrine-disrupting chemicals (EDCs) that are widely utilized as raw materials in the manufacture of dog toy components, and their effects on dog health. To achieve this, we adapted and employed a migration method typically used for children's products to simulate obesogen exposure in dogs through sucking or chewing toys. We demonstrated that out of various obesogens, bisphenol A (BPA) was released from dog toys into synthetic saliva, whereas phthalates and azo dyes were not detected in any of the leachates. Additionally, we found that BPA induced adipogenic differentiation in canine adipose-derived stem cells (cADSCs). Our RNA sequencing experiments revealed that BPA alters the adipogenesis-related gene signature in cADSCs by elevating the expression levels of ADIPOQ, PLIN1, PCK1, CIDEC, and FABP4. The associated transcriptional changes are involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which may contribute to the promotion of adipogenesis by BPA. Our findings suggest that companion dogs are at risk of BPA exposure, which may contribute to obesity in dogs. Therefore, the implementation of precautionary measures is crucial.

mFOLFIRINOX versus mFOLFOX 6 as adjuvant treatment for high-risk stage III colon cancer - the FROST trial: study protocol for a multicenter, randomized controlled, phase II trial.

BACKGROUND: High-risk stage III colon cancer has a considerably poorer prognosis than stage II and low-risk stage III colon cancers. Nevertheless, most guidelines recommend similar adjuvant treatment approaches for all these stages despite the dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis with intensive adjuvant treatment. Given the the proven efficacy of triplet chemotherapy in metastatic colorectal cancer treatment, the goal of this study is to evaluate the oncologic efficacy and safety of mFOLFIRINOX in comparison to those of the current standard of care, mFOLFOX 6, as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer after radical resection. METHODS: This multicenter, randomized (1:1), open-label, phase II trial will assess and compare the effectiveness and toxicity of mFOLFIRINOX and mFOLFOX 6 in patients with high-risk stage III colon cancer after radical resection. The goal of the trial is to enroll 312 eligible patients, from 11 institutes, aged between 20 and 70 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or between 70 and 75 with an ECOG performance status of 0. Patients will be randomized into two arms - Arm A, the experimental arm, and Arm B, the reference arm - and will receive 12 cycles of mFOLFIRINOX and mFOLFOX 6 every 2 weeks, respectively. The primary endpoint of this study is the 3-year disease-free survival, and secondary endpoints include the 3-year overall survival and treatment toxicity. DISCUSSION: The Frost trial would help determine the oncologic efficacy and safety of adjuvant triplet chemotherapy for high-risk stage III colon cancers and ultimately improve prognoses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05179889, registered on 17 December 2021.

Perfluorooctanoic acid inhibits cell proliferation through mitochondrial damage.

Grown evidence has shown that the liver and reproductive organs were the main target organs of perfluorooctanoic acid (PFOA). Herein, we studied a toxic mechanism of PFOA using HeLa Chang liver epithelial cells. When incubated with PFOA for 24 h or 48 h, cell proliferation was inhibited in a concentration- and time-dependent fashion, but interestingly, the feature of dead cells was not notable. Mitochondrial volume was increased with concentration and time, whereas the mitochondrial membrane potential and produced ATP amounts were significantly reduced. Autophagosome-like vacuoles and contraction of the mitochondrial inner membrane were observed in PFOA-treated cells. The expression of acetyl CoA carboxylase (ACC) and p-ACC proteins rapidly decreased, and that of mitochondrial dynamics-related proteins increased. The expression of solute carrier family 7 genes, ChaC glutathione-specific gamma-glutamylcyclotransferase 1, and 5S ribosomal RNA gene was up-regulated the most in cells exposed to PFOA for 24 h, and the KEGG pathway analysis revealed that PFOA the most affected metabolic pathways and olfactory transduction. More importantly, PPAR alpha, fatty acid binding protein 1, and CYP450 family 1 subfamily A member 1 were identified as the target proteins for binding between PFOA and cells. Taken together, we suggest that disruption of mitochondrial integrity and function may contribute closely to PFOA-induced cell proliferation inhibition.

Comparative study on estrogen receptor alpha dimerization and transcriptional activity of parabens.

Parabens are used as preservatives in various household products, including oral products, cosmetics, and hair/body washes. In recent years, the widespread use of parabens has raised concerns due to the potential health risks associated with their estrogenic effects. In the present study, we evaluated and compared the estrogenic activity of parabens using two cell-based in vitro tests: (1) bioluminescence resonance energy transfer (BRET)-based estrogen receptor alpha (ERα) dimerization using HEK293 cells that were stably transfected with ERα-fused NanoLuc luciferase (Nluc) and HaloTag (HT) expression vector, and (2) stably transfected transcriptional activation (STTA) assays using ERα-HeLa9903 cells. The following parabens were tested using the BRET-based ERα dimerization assay and showed estrogenic activity (PC20 values): methyl paraben (MP, 5.98 × 10-5 M), ethyl paraben (EP, 3.29 × 10-5 M), propylparaben (PP, 3.09 × 10-5 M), butyl paraben (BP, 2.58 × 10-5 M), isopropyl paraben (IsoPP, 1.37 × 10-5 M), and isobutyl paraben (IsoBP, 1.43 × 10-5 M). Except MP, all other parabens tested using the STTA assay also showed estrogenic activity: EP, 7.57 × 10-6 M; PP, 1.18 × 10-6 M; BP, 3.02 × 10-7 M; IsoPP, 3.58 × 10-7 M; and IsoBP, 1.80 × 10-7 M. Overall, EP, PP, BP, IsoPP, and IsoBP tested positive for estrogenic activity using both assays. These findings demonstrate that most parabens, albeit not all, induce ERα dimerization and possess estrogenic activity.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus R0 resection for resectable colorectal cancer with peritoneal metastases and low peritoneal cancer index scores: a collaborative observational study from Korea and Japan.

BACKGROUND: The benefits of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) for colorectal cancer with peritoneal metastasis (CPM) remain controversial. R0 resection without peritoneal stripping might be as effective as CRS plus HIPEC. The authors aimed to compare the long-term oncological outcomes of patients with CPM and peritoneal cancer index (PCI) scores less than or equal to 6 who underwent R0 resection in Japan with those who underwent CRS plus HIPEC in Korea. MATERIALS AND METHODS: This international, retrospective cohort study was conducted in Korea and Japan using a prospectively collected clinical database. Patients who underwent surgery from July 2014 to December 2021 for CPM with a PCI score of less than or equal to 6 and completeness of the cytoreduction score-0 were included. The primary outcome was relapse-free survival (RFS), and the secondary outcomes were overall survival, peritoneal RFS (PRFS), and postoperative outcomes. RESULTS: The 3-year RFS was significantly longer in the CRS+HIPEC group than in the R0 resection group: 35.9% versus 6.9% ( P <0.001); 31.0% versus 6.7% ( P =0.040) after propensity score matching. The median PRFS was significantly longer in the CRS+HIPEC group than in the R0 resection group: 24.5 months versus 17.2 months ( P =0.017). The 3-year overall survival and postoperative complications did not significantly differ between the two groups. CONCLUSIONS: RFS and PRFS rates were significantly prolonged after CRS plus HIPEC, whereas postoperative complications and length of hospital stay were not increased. Therefore, curative CRS plus HIPEC may be considered a treatment strategy for selected patients with resectable CPM and low PCI scores.

Characteristics of fall-from-height patients: a retrospective comparison of jumpers and fallers using a multi-institutional registry.

OBJECTIVE: Fall from height (FFH) is a major public health problem that can result in severe injury, disability, and death. This study investigated how the characteristics of jumpers and fallers differ. METHODS: This was a retrospective study of FFH patients enrolled in an Emergency Department-based Injury In-depth Surveillance (EDIIS) registry between 2011 and 2018. Depending on whether the injury was intentional, FFH patients who had fallen from a height of at least 1 m were divided into two groups: jumpers and fallers. Patient characteristics, organ damage, and death were compared between the two groups, and factors that significantly affected death were identified using multivariable logistic analysis. RESULTS: Among 39,419 patients, 1,982 (5.0%) were jumpers. Of the jumpers, 977 (49.3%) were male, while 30,643 (81.9%) of fallers were male. The jumper group had the highest number of individuals in their 20s, with the number decreasing as age increased. In contrast, the number of individuals in the faller group rose until reaching their 50s, after which it declined. More thoracoabdominal, spinal, and brain injuries were found in jumpers. The in-hospital mortality of jumpers and fallers was 832 (42.0%) and 1,268 (3.4%), respectively. Intentionality was a predictor of in-hospital mortality, along with sex, age, and fall height, with an odds ratio of 7.895 (95% confidence interval, 6.746-9.240). CONCLUSION: Jumpers and fallers have different epidemiological characteristics, and jumpers experienced a higher degree of injury and mortality than fallers. Differentiated prevention and treatment strategies are needed for jumpers and fallers to reduce mortality in FFH patients.

Immune Checkpoint-Blocking Nanocages Cross the Blood-Brain Barrier and Impede Brain Tumor Growth.

Glioblastoma (GBM) is the deadliest tumor of the central nervous system, with a median survival of less than 15 months. Despite many trials, immune checkpoint-blocking (ICB) therapies using monoclonal antibodies against the PD-1/PD-L1 axis have demonstrated only limited benefits for GBM patients. Currently, the main hurdles in brain tumor therapy include limited drug delivery across the blood-brain barrier (BBB) and the profoundly immune-suppressive microenvironment of GBM. Thus, there is an urgent need for new therapeutics that can cross the BBB and target brain tumors to modulate the immune microenvironment. To this end, we developed an ICB strategy based on the BBB-permeable, 24-subunit human ferritin heavy chain, modifying the ferritin surface with 24 copies of PD-L1-blocking peptides to create ferritin-based ICB nanocages. The PD-L1pep ferritin nanocages first demonstrated their tumor-targeting and antitumor activities in an allograft colon cancer model. Next, we found that these PD-L1pep ferritin nanocages efficiently penetrated the BBB and targeted brain tumors through specific interactions with PD-L1, significantly inhibiting tumor growth in an orthotopic intracranial tumor model. The addition of PD-L1pep ferritin nanocages to triple in vitro cocultures of T cells, GBM cells, and glial cells significantly inhibited PD-1/PD-L1 interactions and restored T-cell activity. Collectively, these findings indicate that ferritin nanocages displaying PD-L1-blocking peptides can overcome the primary hurdle of brain tumor therapy and are, therefore, promising candidates for treating GBM.

Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: a multicenter, randomized controlled trial (SOLAR trial).

BACKGROUND: Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). METHODS: A multicenter randomized phase II trial involving 364 patients with LARC (cT3-4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45-50.4 Gy in 25-28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2-5 weeks from the last cycle of chemotherapy in the experimental arm and 6-8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. DISCUSSION: This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. TRIAL REGISTRATION: This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.

Fluorescence-guided colorectal surgery: applications, clinical results, and protocols.

In recent years, the rise of minimally invasive surgery has driven the development of surgical devices. Indocyanine green (ICG) fluorescence imaging is receiving increased attention in colorectal surgery for improved intraoperative visualization and decision-making. ICG, approved by the U.S. Food and Drug Administration in 1959, rapidly binds to plasma proteins and is primarily intravascular. ICG absorption of near-infrared light (750-800 nm) and emission as fluorescence (830 nm) when bound to tissue proteins enhances deep tissue visualization. Applications include assessing anastomotic perfusion, identifying sentinel lymph nodes, and detecting colorectal cancer metastasis. However, standardized protocols and research on clinical outcomes remain limited. This study explores ICG's role, advantages, disadvantages, and potential clinical impact in colorectal surgery.

Cyclosporin A inhibits prostate cancer growth through suppression of E2F8 transcription factor in a MELK­dependent manner.

The treatment of advanced prostate cancer remains a formidable challenge due to the limited availability of effective treatment options. Therefore, it is imperative to identify promising druggable targets that provide substantial clinical benefits and to develop effective treatment strategies to overcome therapeutic resistance. Cyclosporin A (CsA) showed an anticancer effect on prostate cancer in cultured cell and xenograft models. E2F8 was identified as a master transcription factor that regulated a clinically significant CsA specific gene signature. The expression of E2F8 increased during prostate cancer progression and high levels of E2F8 expression are associated with a poor prognosis in patients with prostate cancer. MELK was identified as a crucial upstream regulator of E2F8 expression through the transcriptional regulatory network and Bayesian network analyses. Knockdown of E2F8 or MELK inhibited cell growth and colony formation in prostate cancer cells. High expression levels of E2F8 and androgen receptor (AR) are associated with a worse prognosis in patients with prostate cancer compared with low levels of both genes. The inhibition of E2F8 improved the response to AR blockade therapy. These results suggested that CsA has potential as an effective anticancer treatment for prostate cancer, while also revealing the oncogenic role of E2F8 and its association with clinical outcomes in prostate cancer. These results provided valuable insight into the development of therapeutic and diagnostic approaches for prostate cancer.

Impact of Postoperative Naples Prognostic Score to Predict Survival in Patients with Stage II-III Colorectal Cancer.

BACKGROUND: The Naples prognostic score (NPS) is a scoring system that reflects a patient's systemic inflammatory and nutritional status. This study aimed to evaluate whether postoperative NPS is effective in assessing the prognosis of stage II-III colorectal cancer (CRC) patients compared with preoperative NPS. METHODS: Between 2005 and 2012, a total of 164 patients diagnosed with stage II-III CRC, who underwent curative resection followed by adjuvant chemotherapy, were divided into two groups: Group 0-1 (NPS = 0-2) and Group 2 (NPS = 3 or 4). Preoperative NPS was calculated based on the results before surgeries, and postoperative NPS was assessed using the results obtained before adjuvant chemotherapy. RESULTS: The overall survival of Group 0-1 was higher than that of Group 2 in both pre- and postoperative NPS assessments. According to the ROC curve analysis, the Area Under the Curve (AUC) ratio for postoperative NPS was 0.64, compared with 0.57 for preoperative NPS, 0.52 for the preoperative neutrophil-lymphocyte ratio (p = 0.032), and 0.51 for the preoperative platelet-lymphocyte ratio (p = 0.027). CONCLUSIONS: Postoperative NPS is effective in predicting the prognosis of stage II-III CRC patients who underwent curative resection followed by adjuvant chemotherapy. The use of NPS could be beneficial in evaluating the prognosis of CRC patients after surgeries.

Prognostic role of body composition in peritoneal carcinomatosis patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Bioelectric impedance analysis (BIA)-measured body composition and nutritional status have been used as prognostic indicators in various cancer cohorts. This study investigated whether BIA could provide information on prognosis in peritoneal carcinomatosis patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: We retrospectively analyzed the data of 99 patients with preoperative BIA data among those who underwent CRS and HIPEC. The association between BIA-derived parameters and intraoperative peritoneal cancer index (PCI) score was assessed. Predictive analysis for the occurrence of postoperative morbidities including major complications (Clavien-Dindo classification 3-4) and re-admission within 30 days after surgery as well as 1 year mortality was also performed. RESULTS: BIA-derived mineral (r = 0.224, p = 0.027), fat (r = - 0.202, p = 0.048), and total body water (TBW)/fat-free mass (FFM) (r = - 0.280, p = 0.005) showed significant associations with intraoperative PCI score. Lower TBW/FFM was an independent predictor of major postoperative complications (OR 0.047, 95% CI 0.003-0.749, p = 0.031) and re-admission (OR 0.094, 95% CI 0.014-0.657, p = 0.017) within 30 days after surgery. Higher fat mass was also independently associated with a higher risk of major postoperative complications (OR 1.120, 95% CI 1.006-1.248, p = 0.039) and re-admission (OR 1.123, 95% CI 1.024-1.230, p = 0.013). Intraoperative PCI score > 20 (OR 4.489, 95% CI 1.191-16.917, p = 0.027) and re-admission within 30 days after surgery (OR 5.269, 95% CI 1.288-21.547, p = 0.021) independently predicted postoperative 1-year mortality. CONCLUSIONS: We demonstrate that preoperative BIA-derived TBW/FFM and fat mass were significantly correlated with metastatic extent, assessed by PCI score, in patients with peritoneal carcinomatosis. In addition, BIA-derived TBW/FFM and fat mass showed independent predictability for postoperative 30-day major complications and re-admission in patients undergoing CRS and HIPEC. Our findings suggest that assessment of BIA may improve discrete risk stratification in patients who are planned to receive CRS and HIPEC.