Adipose-derived stem cell transplantation enhances spinal cord regeneration by upregulating PGRN expression.

This study aims to investigate the effect of adipose-derived stem cells (ADSCs) transplantation on progranulin (PGRN) expression and functional recovery in rats with spinal cord injury (SCI). ADSCs were isolated from the inguinal adipose tissue of rats. A SCI model was created, and ADSCs were injected into the injured area. Various techniques were used to assess the effects of ADSCs transplantation, including hematoxylin-eosin staining, Masson staining, immunofluorescence staining, electron microscopy, MRI, and motor function assessment. The potential mechanisms of ADSC transplantation were investigated using gene expression analysis and protein analysis. Finally, the safety of this therapy was evaluated through hematoxylin-eosin staining and indicators of liver and kidney damage in serum. PGRN expression increased in the injured spinal cord, and ADSCs transplantation further enhanced PGRN levels. The group that received ADSCs transplantation showed reduced inflammation, decreased scar formation, increased nerve regeneration, and faster recovery of bladder function. Importantly, motor function significantly improved in the ADSC transplantation group. ADSCs transplantation enhances functional regeneration in SCI by upregulating PGRN expression, reducing inflammation and scar formation, and promoting nerve regeneration and myelin repair. These findings suggest that ADSC transplantation is a potential therapy for SCI.

Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) experience in patients with recurrent low grade serous ovarian carcinoma (LGSOC): sub-cohort report of phase 1 clinical trial.

Introduction: Low grade serous ovarian carcinoma (LGSOC) is a rare subtype of ovarian cancer (OC) that is challenging to treat due to its relative chemoresistance. Given that LGSOC patients often recur in the peritoneal cavity, novel intraperitoneal (IP) chemotherapy should be explored. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a method that has demonstrated peritoneal disease control in cancers with peritoneal metastases. Methods: NCT04329494 is a US multicenter phase 1 trial evaluating the safety of PIPAC in recurrent ovarian, uterine, and GI cancers with peritoneal metastases. This analysis describes the outcomes of a sub-cohort of four LGSOC patients treated with IP cisplatin 10.5 mg/m2, doxorubicin 2.1 mg/m2 PIPAC q4-6 weeks. Primary endpoints included dose-limiting toxicities (DLT) and incidence of adverse events (AE). Secondary endpoints were progression free survival (PFS) and treatment response based on radiographic, intraoperative, and pathological findings. Results: Four patients with LGSOC were enrolled of which three were heavily pretreated. Median prior lines of therapy was 5 (range 2-10). Three patients had extraperitoneal metastases, and two patients had baseline partial small bowel obstructive (SBO) symptoms. Median age of patients was 58 (38-68). PIPAC completion rate (≥2 PIPACs) was 75%. No DLTs or Clavien-Dindo surgical complications occurred. No G4/G5 AEs were observed, and one G3 abdominal pain was reported. One patient had a partial response after 3 cycles of PIPAC and completed an additional 3 cycles with compassionate use amendment. Two patients came off study after 2 cycles due to extraperitoneal progressive disease. One patient came off study after 1 cycle due to toxicity. Median decrease in peritoneal carcinomatosis index between cycles 1 and 2 was 5.0%. Ascites decreased in 2 out of 3 patients who had ≥2 PIPACs. Median PFS was 4.3 months (1.7-21.6), median overall survival was 11.6 months (5.4-30.1), and objective response rate was 25%. Conclusion: PIPAC with cisplatin/doxorubicin is well tolerated in LGSOC patients without baseline SBO symptoms. IP response was seen in 2 out of 3 patients that completed ≥2 PIPAC cycles. Further study of PIPAC for patients with recurrent disease limited to the IP cavity and with no partial SBO symptoms should be considered.

Effects of Perfluorohexane Sulfonate Exposure on Immune Cell Populations in Naive Mice.

Perfluorohexane sulfonate (PFHxS) is a member of the per- and polyfluoroalkyls (PFAS) superfamily of molecules, characterized by their fluorinated carbon chains and use in a wide range of industrial applications. PFHxS and perfluorooctane sulfonate are able to accumulate in the environment and in humans with the approximated serum elimination half-life in the range of several years. More recently, some PFAS compounds have also been suggested as potential immunosuppressants. In this study, we analyze immune cell numbers in mice following 28-d repeated oral exposure to potassium PFHxS at 12, 120, 1,200, and 12,000 ng/kg/d, with resulting serum levels ranging up to ∼1,600 ng/ml, approximating ranges found in the general population and at higher levels in PFAS workers. The immunosuppressant cyclophosphamide was analyzed as a positive control. B cells, T cells, and granulocytes from the bone marrow, liver, spleen, lymph nodes, and thymus were evaluated. We found that at these exposures, there was no effect of PFHxS on major T or B cell populations, macrophages, dendritic cells, basophils, mast cells, eosinophils, neutrophils, or circulating Ab isotypes. By contrast, mice exposed to cyclophosphamide exhibited depletion of several granulocyte and T and B cell populations in the thymus, bone marrow, and spleen, as well as reductions in IgG1, IgG2b, IgG2c, IgG3, IgE, and IgM. These data indicate that exposures of up to 12,000 ng/kg of PFHxS for 28 d do not affect immune cell numbers in naive mice, which provides valuable information for assessing the risks and health influences of exposures to this compound.

Treatment with autophagic inhibitors enhances oligonol­induced apoptotic effects in nasopharyngeal carcinoma cells.

Although the combination of chemotherapy and radiotherapy has increased the survival rate of patients with nasopharyngeal carcinoma (NPC), certain patients do not respond well to the treatment and have a poor prognosis. Therefore, novel therapeutic drugs and strategies to improve prognosis of patients with NPC are required. As certain plant extracts can suppress the viability of cancer cells, the present study investigated whether oligonol, a polyphenolic compound primarily found in lychee fruit, exerts anticancer activities in NPC cells. MTT, ELISA and immunoblotting were performed to investigate cell survival, cytokeratin-18 fragment release, and the expression of apoptosis and autophagy markers, respectively. Oligonol decreased the viability of NPC-TW01 and NPC/HK1NPC cell lines. Oligonol increased the protein expression of several apoptosis markers, including cleaved caspase-8 and -3, cleaved PARP and cytokeratin 18 fragment. Moreover, it also increased expression of autophagy markers Beclin 1 and LC3-II, as well as LC3-II/LC3-I ratio in both NPC cell lines. Furthermore, treatment with autophagy inhibitors 3-methyladenine or LY294002 significantly increased oligonol-induced viability inhibition in NPC-TW01 cells. Combined treatment of oligonol + LY294002 reduced LC3-II expression and the LC3II/LC3I ratio while increasing cleaved caspase-8 and -3, cleaved PARP and cytokeratin 18 fragment expression in NPC-TW01 cells. These findings indicated autophagy inhibitors could enhance viability inhibition and apoptotic effects induced by oligonol in NPC cells.

Exploring markers of immunoresponsiveness in papillary thyroid carcinoma and future treatment strategies.

BACKGROUND: The study summarizes the potential use of immunotherapy for BRAF-mutated papillary thyroid cancer (PTC) by analyzing the immune profile of City of Hope PTC patient samples and comparing them to the thyroid dataset available in the TCGA database. MATERIALS AND METHODS: PTC cases with available formalin-fixed paraffin-embedded archived tumor tissue were identified. RNA was extracted from the tumor tissue and analyzed by NanoString to evaluate their immune gene expression profile. Immunohistochemistry was used to determine the expression of immune suppressive genes and lymphocytic infiltration into the tumor tissue. Thyroid cancer cell lines (MDA-T32, MDA-T68, MDA-T85, and MDA-T120) were used to determine the correlation between the BRAF inhibition and CD274 expression. RESULTS: The study found that PTC cases with BRAF mutations had higher expression of immune checkpoint markers CD274 and CTLA4, as well as higher tumor-infiltrating lymphocytes, particularly CD4+T cells. Additionally, the study identified immunosuppressive markers expressed by tumor cells like CD73, CD276, and CD200 that could be targeted for immunotherapy. Further experiments using PTC cell lines lead to the conclusion that CD274 expression correlates with BRAF activity and that inhibitors of BRAF could potentially be used in combination with immunotherapy to treat PTC. CONCLUSIONS: These findings suggest that PTC cases with BRAF mutations or high expression may be correlated with an immune hot signature and could benefit from immunotherapeutic strategies.

Preparation of Mn/TiO2 catalysts using recovered manganese from spent alkaline batteries for low-temperature NH3-SCR.

Black mass (BM) from spent alkaline Zn-MnO2 batteries was used for the first time as a Mn source in the preparation of Mn/TiO2 catalysts for low-temperature NH3-selective catalytic reduction (SCR) of NOx. To recover Mn species and eliminate alkali and Zn species, BM powder underwent DI-water washing, followed by carbothermal reduction. The resulting slags were further dissolved in HNO3, loaded onto TiO2 particles with ball milling, and then subjected to calcination. Nearly 100% of Zn species were removed from the BM via carbothermal reduction at 950 °C for 4 h with 5.0 wt% activated carbon. The resulting catalyst, derived from the treated BM, achieved similar NOx conversion (97%) as the catalyst prepared using a reagent-grade Mn chemical at 160 °C but a higher NOx-to-N2 conversion rate at 78%. The promoted N2 selectivity was attributed to a high Mn4+/Ti ratio and the presence of impurities from BM, such as Fe3+ ions, which enhanced oxidation ability of the catalyst. Conversely, insufficient removal of Zn or carbon additives in the slags led to a decreased Mn concentration, an increased proportion of Mn2+/Mn3+ species, increased surface OH groups, and reduced oxidation ability on the surface, thus reducing NOx conversion and N2 selectivity.

The economic burden of burned patients for hospitalization in Canada.

BACKGROUND: Burn injuries pose a significant burden on both patients and healthcare systems. Yet, costs arising from the consumption of resources by these patients are rarely examined in Canada. OBJECTIVE: The objective of this study was to assess real-world costs resulting from the initial hospitalization of patients admitted to a major burn unit in Quebec, Canada. METHODS: A cost study based on a retrospective cohort was undertaken using in-hospital economic data matched to hospital chart data. Our cohort included all burn-injured patients admitted between April 1, 2017, and March 31, 2021, to the hospital's major burn unit during their initial hospitalization. Descriptive statistics were tabulated for sociodemographic and economic data. Costing data were analyzed unstratified and stratified according to burn severity (i.e., ≥ 20% of total body surface area [TBSA] vs. < 20%). Costs were presented in CAD 2021. RESULTS: Our cohort included 362 patients, including 65 (18%) with TBSA ≥ 20%. The average initial hospitalization cost was $32,360 ($22,783 for < 20% TBSA and $76,121 for ≥ 20% TBSA). CONCLUSION: Findings reveal that the total cost of the initial hospitalization, from a public hospital perspective, was $11,714,348. Our study underlines the substantial burden associated with burns and highlights the need for long-term cost evaluations.

Exploring the Prevalence of Post-traumatic Stress Disorder and Post-traumatic Stress Symptoms in Parents Within 12 Months of Child Burn Injury: A Systematic Review.

Our systematic review aimed to investigate the prevalence of post-traumatic stress symptoms (PTSS) and post-traumatic stress disorder (PTSD) among parents within 12 months of their child's burn injury. A literature search was conducted in PubMed, Embase, Web of Science, Psychinfo, and CINAHL on January 6, 2023, for quantitative studies reporting the prevalence of PTSD and/or PTSS in parents within 12 months following their child's burn injury. The risk of bias was assessed using the Mixed Methods Appraisal Tool version 2018. A narrative synthesis of prevalence was presented. We identified 15 articles that met our inclusion criteria. The prevalence of PTSS within 12 months following the burn injury ranged from 6% to 49%. Prevalence estimates of PTSD within the 12 months following a burn injury were limited, ranging from 4.4% to 22%. Our findings highlight the significant impact of burn injuries on parental mental health, with a considerable proportion of parents experiencing PTSS within 12 months following their child's burn injury. Prevalence estimates for PTSD were limited and warrant further investigation. Our review also underscores the need for standardization of PTSS/PTSD terminology. Timely and targeted psychological support is needed for parents in the aftermath of their child's burn injury.

Social acceptability of psilocybin-assisted therapy for existential distress at the end of life: A population-based survey.

BACKGROUND: Internationally, there is a growing interest in the potential benefits of psilocybin-assisted therapy to treat existential distress at the end of life. However, the social acceptability of this therapy is not yet well known. AIM: This study assesses the social acceptability of the medical use of psilocybin to treat existential distress at the end of life. DESIGN: An online survey was conducted in Canada between November 23 and December 4, 2022. The questionnaire included items pertaining to perceptions, attitudes and concerns towards psilocybin-assisted therapy to treat existential distress at the end of life. PARTICIPANTS: The sample (n = 2800) was stratified by province, age and sex. Participants were adults from four provinces of Canada: Québec, Ontario, Alberta and British Columbia. RESULTS: Overall, 79.3% considered psilocybin-assisted therapy a reasonable medical choice for a patient suffering from existential distress at the end of life, 84.8% agreed that the public health system should cover the costs of the intervention and 63.3% would welcome the legalisation of psilocybin for medical purposes. Previous psilocybin use (p < 0.0001, for all dependent variables), exposure to palliative care (p < 0.05, for all dependent variables) and a progressive political orientation (p < 0.05, for all dependent variables) were associated with more favourable attitudes towards psilocybin-assisted therapy at the end of life. CONCLUSION: The social acceptability of psilocybin-assisted therapy for existential distress at the end of life is rather high in Canada. These findings may contribute to efforts to mobilise resources and improve access to this emerging therapy in palliative and end of life care settings.

Retinal pigment epithelium tear in an idiopathic acute onset bullous central serous chorioretinopathy.

Although retinal pigment epithelium (RPE) tears are common in patients with chronic conditions such as exudative age-related macular degeneration or may occur in response to anti-vascular endothelial growth factor or laser treatment, a spontaneous RPE tear can occur in patients with acute and new-onset bullous central serous chorioretinopathy (CSCR). We present a rare case of a healthy young Asian man with unilateral massive subretinal fluid (SRF). An idiopathic acute-onset bullous CSCR with an RPE tear was diagnosed through ancillary examinations. This patient exhibited good visual recovery as indicated by foveal sparing, spontaneous resolution of SRF, and the lack of a need for unnecessary surgery.

A microgel of CdSe quantum dots for fluorescent bisphenol A detection.

A fluorescent microgel for BPA detection has been successfully prepared by cross-linking linear poly(styrene-co-glycidyl methacrylate) (poly (STY-co-GMA)) with L-cysteine-capped CdSe quantum dots (Lcys-caped CdSe QDs). The microgel contained specific binding sites created by the covalent grafting of the copolymer onto the QDs via the GMA units, allowing for selective trapping of BPA molecules through π-π and hydrogen bond interactions with phenyl, carboxylic, and amine groups. After binding, electron transfer from the QDs to the analyte quenched the fluorescence at a wavelength of 547 nm when excited at 400 nm. The rational compositional and structural design allows the microgel to accurately detect BPA concentrations over a wide dynamic range of 1.0×10-1 to 1.0×105 µg/L with a low detection limit (7.0×10-2 to 8.0×10-2 µg/L) in deionized, drinking, and tap waters within just 2.0 min. On top of that, the sensitivity for BPA detection was 2.0-4.6 times higher than that of the other 3 structural analogues, even molecular imprinting was not involved. The influence of the STY/GMA compositions in the copolymers and environmental conditions, including pH and ionic strength, on the sensing performance was determined. Moreover, the sensing mechanism and the selectivity with respect to the molecular features were elucidated.

Safety and Efficacy of Oxaliplatin Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) in Colorectal and Appendiceal Cancer with Peritoneal Metastases: Results of a Multicenter Phase I Trial in the USA.

BACKGROUND: Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a laparoscopic locoregional treatment for peritoneal metastases (PM) from colorectal cancer (CRC) or appendiceal cancer (AC) in patients who cannot undergo cytoreductive surgery (CRS). While PIPAC has been studied in Europe and Asia, it has not been investigated in the USA. PATIENTS AND METHODS: We evaluated PIPAC with 90 mg/m2 oxaliplatin alone (cycle 1) and preceded by systemic chemotherapy with fluorouracil (5-FU) and leucovorin (LV) (cycle 2-3) as a multicenter prospective phase I clinical trial (NCT04329494). The primary endpoint was treatment-related adverse events (AEs). Secondary endpoints included survival and laparoscopic, histologic, and radiographic response. RESULTS: 12 patients were included: 8 with CRC and 4 with AC. Median prior chemotherapy cycles was 2 (interquartile range (IQR) 2-3). All patients were refractory to systemic oxaliplatin-based chemotherapy. Median peritoneal carcinomatosis index (PCI) was 28 (IQR 19-32). Six (50%) of twelve patients completed three PIPAC cycles. No surgical complications or dose-limiting toxicities were observed. Two patients developed grade 3 treatment-related toxicities (one abdominal pain and one anemia). Median overall survival (OS) was 12.0 months, and median progression-free survival (PFS) was 2.9 months. OS was correlated with stable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria but not with laparoscopic response by PCI or histologic response by peritoneal regression grading system (PRGS). CONCLUSIONS: This phase I trial in the USA demonstrated safety, feasibility, and early efficacy signal of PIPAC with oxaliplatin and chemotherapy in patients with PM from AC or CRC who are refractory to standard lines of systemic chemotherapy.

miR-145a-5p/Plexin-A2 promotes the migration of OECs and transplantation of miR-145a-5p engineered OECs enhances the functional recovery in rats with SCI.

BACKGROUND: Olfactory ensheathing cells (OECs) serve as a bridge by migrating at the site of spinal cord injury (SCI) to facilitate the repair of the neural structure and neural function. However, OEC migration at the injury site not only faces the complex and disordered internal environment but also is closely associated with the migration ability of OECs. METHODS: We extracted OECs from the olfactory bulb of SD rats aged <7 days old. We verified the micro ribonucleic acid (miR)-145a-5p expression level in the gene chip after SCI and OEC transplantation using quantitative reverse transcription (qRT)-polymerase chain reaction (PCR). The possible target gene Plexin-A2 of miR-145a-5p was screened using bioinformatics and was verified using dual-luciferase reporter assay, Western blot, and qRT-PCR. The effect of miR-145a-5p/plexin-A2 on OEC migration ability was verified by wound healing assay, Transwell cell migration assay, and immunohistochemistry. Nerve repair was observed at the injured site of the spinal cord after OEC transplantation using tissue immunofluorescence and magnetic resonance imaging, diffusion tensor imaging, and the Basso-Beattie-Bresnahan locomotor rating scale were further used for imaging and functional evaluation. RESULTS: miR-145a-5p expression in the injured spinal cord tissue after SCI considerably decreased, while Plexin-A2 expression significantly increased. OEC transplantation can reverse miR-145a-5p and Plexin-A2 expression after SCI. miR-145a-5p overexpression enhanced the intrinsic migration ability of OECs. As a target gene of miR-145a-5p, Plexin-A2 hinders OEC migration. OEC transplantation overexpressing miR-145a-5p after SCI can increase miR-145a-5p levels in the spinal cord, reduce Plexin-A2 expression in the OECs and the spinal cord tissue, and promote OEC migration and distribution at the injured site. OEC transplantation overexpressing miR-145a-5p can promote the repair of neural morphology and neural function. CONCLUSIONS: Our study demonstrated that miR-145a-5p could promote OEC migration by down-regulating the target gene Plexin-A2, and transplantation of miR-145a-5p engineered OECs was beneficial to enhance neural structural and functional recovery in SCI rats.

Complete mimicry: Rhabdomyosarcoma with FUS::TFCP2 fusion masquerading as carcinoma-diagnostic challenge and report of two cases.

Rhabdomyosarcomas (RMS) are malignant mesenchymal tumors with skeletal muscle differentiation which are classified into alveolar, embryonal, pleomorphic, and spindle cell/sclerosing RMS. Within the spindle cell/sclerosing RMS tumor type there is a recently recognized sub-type categorized as intraosseous spindle cell RMS with TFCP2/NCOA2 gene fusion. This rare tumor is highly aggressive with predominant involvement of the craniofacial and pelvic bones with approximately 30 cases reported to date. Histopathologic features include spindle cell and epithelioid morphology with a characteristic co-expression of epithelial markers, myogenic markers, and ALK1 expression. We report two cases of gnathic spindle cell/sclerosing RMS with FUS::TFCP2 gene fusion that were initially interpreted as carcinomas by referring institutions and later reclassified when encountered in our practice after additional work-up and molecular characterization.

Effects of PFOS and cyclophosphamide exposure on immune homeostasis in mice.

Perfluorooctane sulfonic acid (PFOS) is member of a class of molecules with fluorinated carbon chains known as polyfluoroalkyls. PFOS have been used to produce a variety of industry and comsumer uses. However, a significant concern is that it accumulates in the environment, including in animals and humans, and that it is a potential immunosuppressant. Here we analyze immune homeostasis in mice following chronic exposure to PFOS at levels up to those historically found in PFOS manufacturing workers. Mice were exposed to 0.15, 1.5, 15, or 50 µg /kg of PFOS for 28 days, after which, B cells, T cells, and granulocytes from the bone marrow, liver, spleen, lymph nodes, and thymus were evaluated. We find that at these exposures, there was no effect of PFOS on major T- or B-cell populations, macrophages, dendritic cells, basophils, mast cells, eosinophils, neutrophils, serum antibodies or select serum cytokines. By contrast, mice exposed the known immunosuppressant cyclophosphamide, which was given at 40 mg/kg for four days, exhibited depletion of several granulocyte, T- and B-cell populations of the thymus, bone marrow, and spleen, as well as circulating IgM and IgE antibodies. These data indicate that exposures of up to 50 µg /kg of PFOS for 28 days does not affect immune homeostasis in mice.

Single-cell transcriptomic analysis of normal and pathological tissues from the same patient uncovers colon cancer progression.

The aim of the present study was to elucidate the evolutionary trajectory of colon cells from normal colon mucosa, to adenoma, then to carcinoma in the same microenvironment. Normal colon, adenoma and carcinoma tissues from the same patient were analyzed by single-cell sequencing, which perfectly simulated the process of time-dependent colon cancer due to the same microenvironment. A total of 22 cell types were identified. Results suggest the presence of dominant clones of same cells including C2 goblet cell, epithelial cell subtype 1 (Epi1), enterocyte cell subset 0 (Entero0), and Entero5 in carcinoma. Epi1 and Entero0 were Co-enriched in antibacterial and IL-17 signaling, Entero5 was enriched in immune response and mucin-type O-glycan biosynthesis. We discovered new colon cancer related genes including AC007952.4, NEK8, CHRM3, ANO7, B3GNT6, NEURL1, ODC1 and KCNMA1. The function of TBC1D4, LTB, C2CD4A, AND GBP4/5 in T cells needs to be clarified. We used colon samples from the same person, which provide new information for colon cancer therapy.