Comedones and epidermal cysts on the abdominal skin of a dog occurring after a laparotomy.

An 8-year-old neutered male shih tzu dog underwent laparotomy for cystolithectomy. Ten days later, multiple various-sized cystic nodules were observed on the suture line and surrounding abdominal skin, although the surgical incision had healed well. Microscopically, various-sized cysts lined with thin walls of stratified squamous epithelium in the dermis were dilated and filled with keratin. Adnexal differentiation from the wall was not seen. Thus, the abdominal lesions were diagnosed as comedones and epidermal cysts. Herein, we describe the case of a dog with comedones and epidermal cysts on the abdominal skin after a laparotomy. Key clinical message: Multiple various-sized cystic lesions of the follicles are described. The implantation of epidermal fragments into the dermis by surgery may induce epidermal cysts and comedones in the skin of hyperadrenocorticism-affected dogs.

Comédons et kystes épidermiques sur la peau abdominale d'un chien survenant après une laparotomie. Un chien shih tzu mâle castré de 8 ans a subi une laparotomie pour cystolithectomie. Dix jours plus tard, de multiples nodules kystiques de différentes tailles ont été observés sur la ligne de suture et sur la peau abdominale environnante, bien que l'incision chirurgicale ait bien cicatrisé. Au microscope, des kystes de différentes tailles bordés de fines parois d'épithélium pavimenteux stratifié dans le derme étaient dilatés et remplis de kératine. Aucune différenciation annexielle par rapport à la paroi n'a été observée. Ainsi, les lésions abdominales ont été diagnostiquées comme des comédons et des kystes épidermiques. Nous décrivons ici le cas d'un chien présentant des comédons et des kystes épidermiques sur la peau abdominale après une laparotomie.Message clinique clé:De multiples lésions kystiques des follicules, de différentes tailles, sont décrites. L'implantation chirurgicale de fragments d'épiderme dans le derme peut provoquer des kystes épidermiques et des comédons dans la peau des chiens atteints d'hypercorticisme.(Traduit par Dr Serge Messier).

Enhanced mucosal mitochondrial function corrects dysbiosis and OXPHOS metabolism in IBD.

Background: Mitochondrial (Mito) dysfunction in IBD reduces mucosal O2 consumption and increases O2 delivery to the microbiome. Increased enteric O2 promotes blooms of facultative anaerobes (eg. Proteobacteria ) and restricts obligate anaerobes (eg. Firmicutes ). Dysbiotic metabolites negatively affect host metabolism and immunity. Our novel compound (AuPhos) upregulates intestinal epithelial cell (IEC) mito function, attenuates colitis and corrects dysbiosis in humanized Il10-/- mice. We posit that AuPhos corrects IBD-associated dysbiotic metabolism. Methods: Primary effect of AuPhos on mucosal Mito respiration and healing process was studied in ex vivo treated human colonic biopsies and piroxicam-accelerated (Px) Il10-/- mice. Secondary effect on microbiome was tested in DSS-colitis WT B6 and germ-free 129.SvEv WT or Il10-/- mice reconstituted with human IBD stool (Hu- Il10-/- ). Mice were treated orally with AuPhos (10- or 25- mg/kg; q3d) or vehicle, stool samples collected for fecal lipocalin-2 (f-LCN2) assay and microbiome analyses using 16S rRNA sequencing. AuPhos effect on microbial metabolites was determined using untargeted global metabolomics. AuPhos-induced hypoxia in IECs was assessed by Hypoxyprobe-1 staining in sections from pimonidazole HCl-infused DSS-mice. Effect of AuPhos on enteric oxygenation was assessed by E. coli Nissle 1917 WT (aerobic respiration-proficient) and cytochrome oxidase (cydA) mutant (aerobic respiration-deficient). Results: Metagenomic (16S) analysis revealed AuPhos reduced relative abundances of Proteobacteria and increased blooms of Firmicutes in uninflamed B6 WT, DSS-colitis, Hu-WT and Hu- Il10-/- mice. AuPhos also increased hypoxyprobe-1 staining in surface IECs suggesting enhanced O2 utilization. AuPhos-induced anaerobiosis was confirmed by a significant increase in cydA mutant compared to WT (O2-utlizing) E.coli . Ex vivo treatment of human biopsies with AuPhos showed significant increase in Mito mass, and complexes I and IV. Further, gene expression analysis of AuPhos-treated biopsies showed increase in stem cell markers (Lgr4, Lgr5, Lrig1), with concomitant decreases in pro-inflammatory markers (IL1ß,MCP1, RankL). Histological investigation of AuPhos-fed Px- Il10-/- mice showed significantly decreased colitis score in AuPhos-treated Px- Il10-/- mice, with decrease in mRNA of pro-inflammatory cytokines and increase in Mito complexes ( ND5 , ATP6 ). AuPhos significantly altered microbial metabolites associated with SCFA synthesis, FAO, TCA cycle, tryptophan and polyamine biosynthesis pathways. AuPhos increased pyruvate, 4-hydroxybutyrate, 2-hydroxyglutarate and succinate, suggesting an upregulation of pyruvate and glutarate pathways of butyrate production. AuPhos reduced IBD-associated primary bile acids (BA) with concomitant increase in secondary BA (SBA). AuPhos treatment significantly decreased acylcarnitines and increased L-carnitine reflective of enhanced FAO. AuPhos increases TCA cycle intermediates and creatine, energy reservoir substrates indicating enhanced OxPHOS. Besides, AuPhos also upregulates tryptophan metabolism, decreases Kynurenine and its derivatives, and increases polyamine biosynthesis pathway (Putresceine and Spermine). Conclusion: These findings indicate that AuPhos-enhanced IEC mitochondrial function reduces enteric O2 delivery, which corrects disease-associated metabolomics by restoring short-chain fatty acids, SBA, AA and IEC energy metabolism.

Amoebicidal effect of chlorine dioxide gas against pathogenic Naegleria fowleri and Acanthamoeba polyphaga.

The pathogenic free-living amoebae, Naegleria fowleri and Acanthamoeba polyphaga, are found in freshwater, soil, and unchlorinated or minimally chlorinated swimming pools. N. fowleri and A. polyphaga are becoming problematic as water leisure activities and drinking water are sources of infection. Chlorine dioxide (ClO2) gas is a potent disinfectant that is relatively harmless to humans at the concentration used for disinfection. In this study, we examined the amoebicidal effects of ClO2 gas on N. fowleri and A. polyphaga. These amoebae were exposed to ClO2 gas from a ready-to-use product (0.36 ppmv/h) for 12, 24, 36, and 48 h. Microscopic examination showed that the viability of N. fowleri and A. polyphaga was effectively inhibited by treatment with ClO2 gas in a time-dependent manner. The growth of N. fowleri and A. polyphaga exposed to ClO2 gas for 36 h was completely inhibited. In both cases, the mRNA levels of their respective actin genes were significantly reduced following treatment with ClO2 gas. ClO2 gas has an amoebicidal effect on N. fowleri and A. polyphaga. Therefore, ClO2 gas has been proposed as an effective agent for the prevention and control of pathogenic free-living amoeba contamination.

Structural Color Inks Containing Photonic Microbeads for Direct Writing.

Printing structurally colored patterns is of great importance for providing customized graphics for various purposes. Although a direct writing technique has been developed, the use of colloidal dispersions as photonic inks requires delicate printing conditions and restricts the mechanical and optical properties of printed patterns. In this work, we produce elastic photonic microbeads through scalable bulk emulsification and formulate photonic inks containing microbeads for direct writing. To produce the microbeads, a photocurable colloidal dispersion is emulsified into a highly concentrated sucrose solution via vortexing, which results in spherical emulsion droplets with a relatively narrow size distribution. The microbeads are produced by photopolymerization and are then suspended in urethane acrylate resin at volume fractions of 0.35-0.45. The photonic inks retain high color saturation of the microbeads and offer enhanced printability and dimensional control on various target substrates including fabrics, papers, and even skins. Importantly, the printed graphics show high mechanical stability as the elastic microbeads are embedded in the polyurethane matrix. Moreover, the colors show a wide viewing angle and low-angle dependency due to the optical isotropy of individual microbeads and light refraction at the air-matrix interface. We postulate that this versatile direct writing technique is potentially useful for structural color coating and printing on the surfaces of arbitrary 3D objects.

Current Status of Latent Tuberculosis Infection Treatment Among Pediatric Patients in Korea: Prescription and Treatment Completion.

BACKGROUND: The treatment of pediatric patients with latent tuberculosis infection (LTBI) is a crucial TB control strategy. LTBI is not a reportable communicable disease, and data regarding LTBI treatment in pediatric patients in Korea are scarce. This study aimed to investigate the prescription patterns and treatment completion rates among pediatric patients with LTBI in Korea by analyzing National Health reimbursement claims data. METHODS: We retrospectively analyzed outpatient prescription records for pediatric patients aged 18 or younger with LTBI-related diagnostic codes from 2016 to 2020. We compared the frequency of prescriptions for the standard treatment regimen (9 months of isoniazid [9H]) and an alternative treatment regimen (3 months of isoniazid plus rifampicin [3HR]). We also assessed the treatment incompletion rates by age group, treatment regimen, treatment duration, the level of medical facility, physician's specialty, and hospital location. We performed multivariable analysis to identify factors influencing treatment incompletion. RESULTS: Among the 11,362 patients who received LTBI treatment, 6,463 (56.9%) were prescribed the 9H regimen, while 4,899 (43.1%) received the 3HR regimen. Patients in the 3HR group were generally older than those in the 9H group. The proportion of 3HR regimen prescriptions significantly greater in the later period (2018-2020), in primary hospitals, under the management of non-pediatric specialists, and in metropolitan regions. The overall treatment incompletion rate was 39.7% (9H group: 46.9%, 3HR group: 30.3%). In the multivariable analysis, 9H regimen prescription was the strongest factor associated with treatment incompletion (adjusted odds ratio, 2.42; 95% confidence interval, 2.20-2.66; P < 0.001). Additionally, management in a primary hospital, a hospital's location in a non-metropolitan region, and management by a non-pediatric specialist were also significant risk factors for treatment incompletion. CONCLUSION: Our study results suggest that promoting the use of 3HR regimen prescriptions could be an effective strategy to enhance treatment completion. Physicians in primary hospitals, hospitals located in non-metropolitan regions, and physicians without a pediatric specialty require increased attention when administering LTBI treatment to pediatric patients to ensure treatment completion.

A pontomesencephalic PACAPergic pathway underlying panic-like behavioral and somatic symptoms in mice.

Panic disorder is characterized by uncontrollable fear accompanied by somatic symptoms that distinguish it from other anxiety disorders. Neural mechanisms underlying these unique symptoms are not completely understood. Here, we report that the pituitary adenylate cyclase-activating polypeptide (PACAP)-expressing neurons in the lateral parabrachial nucleus projecting to the dorsal raphe are crucial for panic-like behavioral and physiological alterations. These neurons are activated by panicogenic stimuli but inhibited in conditioned fear and anxiogenic conditions. Activating these neurons elicits strong defensive behaviors and rapid cardiorespiratory increase without creating aversive memory, whereas inhibiting them attenuates panic-associated symptoms. Chemogenetic or pharmacological inhibition of downstream PACAP receptor-expressing dorsal raphe neurons abolishes panic-like symptoms. The pontomesencephalic PACAPergic pathway is therefore a likely mediator of panicogenesis, and may be a promising therapeutic target for treating panic disorder.

YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulation in murine bone development.

Fetal bone development occurs through the conversion of avascular cartilage to vascularized bone at the growth plate. This requires coordinated mobilization of osteoblast precursors with blood vessels. In adult bone, vessel-adjacent osteoblast precursors are maintained by mechanical stimuli; however, the mechanisms by which these cells mobilize and respond to mechanical cues during embryonic development are unknown. Here, we show that the mechanoresponsive transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) spatially couple osteoblast precursor mobilization to angiogenesis, regulate vascular morphogenesis to control cartilage remodeling, and mediate mechanoregulation of embryonic murine osteogenesis. Mechanistically, YAP and TAZ regulate a subset of osteoblast-lineage cells, identified by single-cell RNA sequencing as vessel-associated osteoblast precursors, which regulate transcriptional programs that direct blood vessel invasion through collagen-integrin interactions and Cxcl12. Functionally, in 3D human cell co-culture, CXCL12 treatment rescues angiogenesis impaired by stromal cell YAP/TAZ depletion. Together, these data establish functions of the vessel-associated osteoblast precursors in bone development.

A gold-based inhibitor of oxidative phosphorylation is effective against triple negative breast cancer.

Triple-negative breast cancer (TNBC) is associated with metabolic heterogeneity and poor prognosis with limited treatment options. New treatment paradigms for TNBC remains an unmet need. Thus, therapeutics that target metabolism are particularly attractive approaches. We previously designed organometallic Au(III) compounds capable of modulating mitochondrial respiration by ligand tuning with high anticancer potency in vitro and in vivo. Here, we show that an efficacious Au(III) dithiocarbamate (AuDTC) compound induce mitochondrial dysfunction and oxidative damage in cancer cells. Efficacy of AuDTC in TNBC mouse models harboring mitochondrial oxidative phosphorylation (OXPHOS) dependence and metabolic heterogeneity establishes its therapeutic potential following systemic delivery. This provides evidence that AuDTC is an effective modulator of mitochondrial respiration worthy of clinical development in the context of TNBC. ONE SENTENCE SUMMARY: Metabolic-targeting of triple-negative breast cancer by gold anticancer agent may provide efficacious therapy.

A Study on the Monitoring of Toxocara spp. in Various Children's Play Facilities in the Republic of Korea (2016-2021).

Toxocara spp. is a zoonotic soil-transmitted parasite that infects canids and felids, which causes toxocariasis in humans, migrating to organ systems, including the lungs, the ocular system, and the central nervous system. Since Toxocara spp. is usually transmitted through soil, children tend to be more susceptible to infection. In order to monitor contamination with Toxocara spp. in children's play facilities in the Republic of Korea, we investigated 11,429 samples of soil from daycare centers, kindergartens, elementary schools, and parks across the country from January 2016 to December 2021. Since the Environmental Health Act in the Republic of Korea was enacted in March 2008, there have been sporadic reports of contamination by Toxocara spp. in children's activity zones. In this study, soil from children's play facilities in regions across the Republic of Korea was monitored according to the Korean standardized procedure to use it as basic data for preventive management and public health promotion. The national average positive rate was 0.16% (18/11,429), and Seoul showed a higher rate of 0.63% (2/318) than any other regions while Incheon, Daegu, Ulsan, Kangwon-do, Jeollabuk-do, and Jeollanam-do were negative (p < 0.05). The positive rates were as follows: 0.37% (4/1089) in daycare centers, 0.13% (3/2365) in kindergartens, 0.2% (7/4193) in elementary schools, 0.09% (1/1143) in apartments, and 0.14% (3/2198) in parks. In addition, it was confirmed that 0.2% (1/498) of elementary schools and 1.17% (2/171) of parks were re-contaminated among play facilities managed with the establishment of a regular inspection cycle. Consequently, there is an essential need for continuous monitoring of Toxocara spp. contamination and regular education for preschool and school children in order to prevent soil-borne parasite infections.

Fibrinous pleuritis associated with Streptococcus canis in a leopard cat (Prionailurus bengalensis euptilurus).

Leopard cat (Prionailurus bengalensis euptilurus) is a small wild cat assessed as an endangered wildlife in Korea. There have been very few reports of their diseases. Herein, we describe fibrinous pleuritis caused by Streptococcus canis infection with excessive pleural effusion, hydropericardium, mild ascites, and liver fibrosis in a leopard cat. S. canis is a commensal microflora in domestic cats and often affects the upper respiratory tract inducing chronic and severe respiratory diseases. However, there is no literature regarding the S. canis in leopard cats. Therefore, we first report fibrinous pleuritis associated with an S. canis infection in a leopard cat.

Comparison of the efficacy in improving trigeminal neuralgia in petroclival meningioma between microsurgery and radiosurgery: a meta-analysis.

The purpose of this study was to systematically review studies in the literature to assess the superiority between microsurgery and radiosurgery regarding the efficacy in improving petroclival meningioma (PCM)-related trigeminal neuralgia (TN). PubMed, Embase, Web of Science, and Cochrane clinical trial databases were systematically searched from the inception until December 08, 2022. The overall proportion of patients with improved TN after treatment in all six included studies was 56% (95% confidence interval [CI], 35-76.9%). Higgins I2 statistics showed significant heterogeneity (I2 = 90%). Subgroup analysis showed that the proportion of improved TN was higher in the microsurgery group than that in the radiosurgery group (89%; 95% CI, 81-96.5% vs. 37%, 95% CI, 22-52.7%, respectively, p < 0.01). Subgroup analysis (for studies that documented the number of posttreatment Barrow Neurological Institute scores 1 and 2) revealed that the proportion of pain-free without medication after treatment was higher in the microsurgery group than that in the radiosurgery group (90.7%; 95% CI, 81-99.7% vs. 34.5%, 95% CI, 21.3-47.7.7%, respectively, p < 0.01). Based on the results of this meta-analysis, we concluded that microsurgery is superior to radiosurgery in controlling PCM-related TN.

Three-dimensional label-free morphology of CD8 + T cells as a sepsis biomarker.

Sepsis is a dysregulated immune response to infection that leads to organ dysfunction and is associated with a high incidence and mortality rate. The lack of reliable biomarkers for diagnosing and prognosis of sepsis is a major challenge in its management. We aimed to investigate the potential of three-dimensional label-free CD8 + T cell morphology as a biomarker for sepsis. This study included three-time points in the sepsis recovery cohort (N = 8) and healthy controls (N = 20). Morphological features and spatial distribution within cells were compared among the patients' statuses. We developed a deep learning model to predict the diagnosis and prognosis of sepsis using the internal cell morphology. Correlation between the morphological features and clinical indices were analysed. Cell morphological features and spatial distribution differed significantly between patients with sepsis and healthy controls and between the survival and non-survival groups. The model for predicting the diagnosis and prognosis of sepsis showed an area under the receiver operating characteristic curve of nearly 100% with only a few cells, and a strong correlation between the morphological features and clinical indices was observed. Our study highlights the potential of three-dimensional label-free CD8 + T cell morphology as a promising biomarker for sepsis. This approach is rapid, requires a minimum amount of blood samples, and has the potential to provide valuable information for the early diagnosis and prognosis of sepsis.

The decoy oligodeoxynucleotide against HIF-1α and STAT5 ameliorates atopic dermatitis-like mouse model.

Atopic dermatitis (AD) is a common inflammatory skin disease caused by an immune disorder. Mast cells are known to be activated and granulated to maintain an allergic reaction, including rhinitis, asthma, and AD. Although hypoxia-inducible factor-1 alpha (HIF-1α) and signal transducer and activator of transcription 5 (STAT5) play crucial roles in mast cell survival and granulation, their effects need to be clarified in allergic disorders. Thus, we designed decoy oligodeoxynucleotide (ODN) synthetic DNA, without open ends, containing complementary sequences for HIF-1α and STAT5 to suppress the transcriptional activities of HIF-1α and STAT5. In this study, we demonstrated the effects of HIF-1α/STAT5 ODN using AD-like in vivo and in vitro models. The HIF-1α/STAT5 decoy ODN significantly alleviated cutaneous symptoms similar to AD, including morphology changes, immune cell infiltration, skin barrier dysfunction, and inflammatory response. In the AD model, it also inhibited mast cell infiltration and degranulation in skin tissue. These results suggest that the HIF-1α/STAT5 decoy ODN ameliorates the AD-like disorder and immunoglobulin E (IgE)-induced mast cell activation by disrupting HIF-1α/STAT5 signaling pathways. Taken together, these findings suggest the possibility of HIF-1α/STAT5 as therapeutic targets and their decoy ODN as a potential therapeutic tool for AD.

Predictor of the Postoperative Swelling After Craniotomy for Spontaneous Intracerebral Hemorrhage: Sphericity Index as a Novel Parameter.

Objective: Spontaneous intracerebral hemorrhage is a serious type of stroke with high mortality and disability rates. Surgical treatment options vary; however, predicting edema aggravation is crucial when choosing the optimal approach. We propose using the sphericity index, a measure of roundness, to predict the aggravation of edema and guide surgical decisions. Methods: We analyzed 56 cases of craniotomy and hematoma evacuation to investigate the correlation between the sphericity index and patient outcomes, including the need for salvage decompressive craniectomy (DC). Results: The patients included 35 (62.5%) men and 21 (37.5%) women, with a median age of 62.5 years. The basal ganglia was the most common location of hemorrhage (50.0%). The mean hematoma volume was 86.3 cc, with 10 (17.9%) instances of hematoma expansion. Cerebral herniation was observed in 44 (78.6%) patients, intraventricular hemorrhage in 34 (60.7%), and spot signs in 9 (16.1%). Salvage DC was performed in 13 (23.6%) patients to relieve intracranial pressure. The median follow-up duration was 6 months, with a mortality rate of 12.5%. The sphericity index was significantly correlated with delayed swelling and hematoma expansion but not salvage DC. Conclusions: The sphericity index is a promising predictor of delayed swelling and hematoma expansion that may aid in the development of surgical guidelines and medication strategies. Further large-scale studies are required to explore these aspects and establish comprehensive guidelines.

Immunogenicity and Safety of a Newly Developed Live Attenuated Varicella Vaccine in Healthy Children: A Multi-National, Randomized, Double-Blinded, Active-Controlled, Phase 3 Study.

Korean manufacturers have developed a new varicella vaccine, NBP608. This phase 3, randomized, double-blind, multicenter study aimed to compare the immunogenicity and safety of NBP608 in healthy children to those of VarivaxTM (control). Children aged 12 months to 12 years were randomized in a ratio of 1:1 to receive either NBP608 or the control vaccine. Serum samples were obtained before vaccination and within six to eight weeks after vaccination. In total, 499 participants (NBP608, n = 251; control, n = 248) were enrolled. The seroconversion rate (SCR) measured using a FAMA assay was 99.53% in the NBP608 group, and the lower limit of the 95% confidence interval (95% LCL) for the SCR difference (NBP608 minus the control) was 0.52%. This 95% LCL for the difference was higher than the specified non-inferiority margin of -15%. In an assessment using gpELISA, the SCR was 99.53% in the NBP608 group, and the 95% LCL for the SCR difference was 6.5%, which was higher than the specified non-inferiority margin of -15%. There were no significant differences between the NBP608 and control group with respect to the proportions of participants who demonstrated local and systemic solicited AEs. This study indicated that NBP608 had a clinically acceptable safety profile and was not immunologically inferior to VarivaxTM.

Nemopilema nomurai jellyfish venom attenuates phenotypic modulation of PDGF BB-induced vascular smooth muscle cells and κ-carrageenan-induced rat tail thrombosis.

Jellyfish venoms have long been recognized as a potentially rich source of natural bioactive compounds with pharmacological potential for the creation of innovative drugs. Our previous study demonstrated that Nemopilema nomurai jellyfish venom (NnV) has a chymotrypsin-like serine protease with fibrinolytic activity in vitro. Therefore, the present study aims to investigate the potential effect of NnV on cell migration, proliferation, and differentiation of vascular smooth muscle cells (VSMC; A7r5 cells) involved in the probable mechanism pathways. We also determined its anti-thrombotic effect through κ-carrageenan-induced Sprague-Dawley (SD) rat tail thrombus model. NnV inhibits on Platelet-derived growth factor (PDGF)-BB-stimulated A7r5 cells migration and proliferation by decreasing matrix metalloproteinase 2 (MMP-2) level and phosphorylation of ERK and Akt in a dose-dependent manner, but not p38. Furthermore, NnV regulates the phenotype transition of differentiation in PDGF-BB-stimulated A7r5 cells via ɑ-SMA and calponin in a dose-dependent manner. In an in vivo study, NnV treatment demonstrated clear anti-thrombotic activity in a dose-dependent manner, which was associated with decreased thrombus formation and length in κ-carrageenan-induced SD rat tail. These findings suggested that NnV has a novel fibrinolytic enzyme that can be used to prevent and/or treat thrombosis-related cardiovascular disorders.

KRAS activation in gastric cancer stem-like cells promotes tumor angiogenesis and metastasis.

Our previous work showed that KRAS activation in gastric cancer cells leads to activation of an epithelial-to-mesenchymal transition (EMT) program and generation of cancer stem-like cells (CSCs). Here we analyze how this KRAS activation in gastric CSCs promotes tumor angiogenesis and metastasis. Gastric cancer CSCs were found to secrete pro-angiogenic factors such as vascular endothelial growth factor A (VEGF-A), and inhibition of KRAS markedly reduced secretion of these factors. In a genetically engineered mouse model, gastric tumorigenesis was markedly attenuated when both KRAS and VEGF-A signaling were blocked. In orthotropic implant and experimental metastasis models, silencing of KRAS and VEGF-A using shRNA in gastric CSCs abrogated primary tumor formation, lymph node metastasis, and lung metastasis far greater than individual silencing of KRAS or VEGF-A. Analysis of gastric cancer patient samples using RNA sequencing revealed a clear association between high expression of the gastric CSC marker CD44 and expression of both KRAS and VEGF-A, and high CD44 and VEGF-A expression predicted worse overall survival. In conclusion, KRAS activation in gastric CSCs enhances secretion of pro-angiogenic factors and promotes tumor progression and metastasis.

Engineered Extracellular Vesicles with Compound-Induced Cargo Delivery to Solid Tumors.

Efficient delivery of functional factors into target cells remains challenging. Although extracellular vesicles (EVs) are considered to be potential therapeutic delivery vehicles, a variety of efficient therapeutic delivery tools are still needed for cancer cells. Herein, we demonstrated a promising method to deliver EVs to refractory cancer cells via a small molecule-induced trafficking system. We generated an inducible interaction system between the FKBP12-rapamycin-binding protein (FRB) domain and FK506 binding protein (FKBP) to deliver specific cargo to EVs. CD9, an abundant protein in EVs, was fused to the FRB domain, and the specific cargo to be delivered was linked to FKBP. Rapamycin recruited validated cargo to EVs through protein-protein interactions (PPIs), such as the FKBP-FRB interaction system. The released EVs were functionally delivered to refractory cancer cells, triple negative breast cancer cells, non-small cell lung cancer cells, and pancreatic cancer cells. Therefore, the functional delivery system driven by reversible PPIs may provide new possibilities for a therapeutic cure against refractory cancers.

The significance of decompressive craniectomy for older patients with traumatic brain injury: a propensity score matching analysis from large multi-center data.

The efficacy of decompressive craniectomy (DC) for traumatic brain injury (TBI) have been investigated in two recent randomized clinical trials (RCTs) and DC is recommended as an optional treatment for improving overall survival compared to medical treatment. However, the two RCTs enrolled extremely young adults, and the efficacy of DC in older adults remains questionable. Therefore, to identify the efficacy of DC in older adults, we compared patients who received medical care with those who underwent DC after propensity score matching (PSM). From the Korea Multi-center Traumatic Brain Injury Database, 443 patients identified as having intracranial hypertension and a necessity of DC were retrospectively enrolled. The patients were classified into the DC (n = 375) and non-DC (n = 68) groups according to operation records. The PSM was conducted to match the patients in the DC group with those receiving medical care (non-DC). After PSM, the newly matched group (DC, n = 126) was compared with patients without DC (non-DC, n = 63). The mean difference in the logit of the propensity scores (LPS) was 0.00391 and the mean age of enrolled patients were 65 years. The results of the comparative analyses after PSM showed that the 6-month mortality rate of the non-DC group was higher than that of the DC group (61.9% vs. 51.6%, p = 0.179). In terms of favorable outcomes (modified Rankin Scale [mRS] score < 4), the DC group showed a lower rate of favorable mRS scores (11.9% vs. 17.5%, p = 0.296) than the non-DC group.