Modeling gastric intestinal metaplasia in 3D organoids using nitrosoguanidine.

Gastric intestinal metaplasia (GIM) represents a precancerous stage characterized by morphological and pathophysiological changes in the gastric mucosa, where gastric epithelial cells transform into a phenotype resembling that of intestinal cells. Previous studies have demonstrated that the intragastric administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces both gastric carcinoma and intestinal metaplasia in mice. Here, we show that MNNG induces GIM in three-dimensional (3D) mouse organoids. Our histological analyses reveal that MNNG-induced gastric organoids undergo classical morphological alterations, exhibiting a distinct up-regulation of CDX2 and MUC2, along with a down-regulation of ATP4B and MUC6. Importantly, metaplastic cells observed in MNNG-treated organoids originate from MIST1+ cells, indicating their gastric chief cell lineage. Functional analyses show that activation of the RAS signaling pathway drives MNNG-induced metaplasia in 3D organoids, mirroring the characteristics observed in human GIM. Consequently, modeling intestinal metaplasia using 3D organoids offers valuable insights into the molecular mechanisms and spatiotemporal dynamics of the gastric epithelial lineage during the development of intestinal metaplasia within the gastric mucosa. We conclude that the MNNG-induced metaplasia model utilizing 3D organoids provides a robust platform for developing preventive and therapeutic strategies to mitigate the risk of gastric cancer before precancerous lesions occur.

Effects of a High Trans Fatty Acid Diet on Kidney-, Liver-, and Heart-Associated Diseases in a Rabbit Model.

Trans fatty acids are specific unsaturated fats found in processed foods that undergo hydrogenation, leading to hepatic disorders such as metabolic-associated fatty liver disease (MAFLD) and conditions like CVD and CKD. The effects of different food samples containing trans fatty acids (elaidic and oleic acid) on the liver, heart, and kidney through antioxidant enzyme activity were investigated in animal models. Liver function tests (ALT, ALP, AST, and LDH), heart biomarker levels (CPK, TC, HDL, LDL, and triglycerides), and kidney biomarker levels (serum creatinine, blood urea nitrogen, and serum uric acid) were examined in serum of rabbits and the histopathology of liver tissues. Results showed that these biomarkers were more elevated in the Mujahid Ghee group than in the normal control, oleic acid, and Kausar Ghee groups. The concentration of antioxidant markers such as peroxidase, glutathione, catalase, thiobarbituric acid reactive substances, and superoxide dismutase were lower in the Mujahid Ghee group. HPLC showed that Mujahid Ghee had the highest quantified value of elaidic acid among all selected samples. Overall, this study demonstrated that elaidic acid in its purest form aggravated MAFLD in rabbit livers and provoked CVK and CVD.

Analysis of the complete mitochondrial genome of Panax quinquefolius reveals shifts from cis-splicing to trans-splicing of intron cox2i373.

Panax quinquefolius is a perennial plant with medicinal values. In this study, we assembled the complete mitochondrial genome (mitogenome) of P. quinquefolius using PMAT assembler. The total length of P. quinquefolius mitogenome is 573,154 bp. We annotated a total of 34 protein-coding genes (PCGs), 35 tRNA genes, and 6 rRNA genes in this mitogenome. The analysis of repetitive elements shows that there are 153 SSRs, 24 tandem repeats and 242 pairs of dispersed repeats this mitogenome. Also, we found 24 homologous sequences with a total length of 64,070 bp among its mitogenome and plastome, accounting for 41.05 % of the plastome, and 11.18 % of the mitogenome, showing a remarkable frequent sequence dialogue between plastome and mitogenomes. Besides, a total of 583 C to U RNA editing sites on 34 PCGs of high confidence were predicted by using Deepred-mt. We also inferred the phylogenetic relationships of P. quinquefolius and other angiosperms based on mitochondrial PCGs. Finally, we observed a shift from cis- to trans-splicing in P. quinquefolius for two mitochondrial introns, namely cox2i373 and nad1i728, and a pair of 48 bp short repetitive sequences may be associated with the breaking and rearrangement of the cox2i373 intron. The fragmentation of the cox2i373 intron was further confirmed by our PCR amplification experiments. In summary, our report on the P. quinquefolius mitogenome provides a new perspective on the intron evolution of the mitogenome.

All trans retinoic acid-induced bilateral disc edema in a case of acute promyelocytic leukemia.

An 18-year-old female presented with sudden onset bilateral vision loss. Extensive retinal hemorrhages were seen in both eyes. Systemic examination lead to a diagnosis of acute promyelocytic leukemia. The patient was treated with all trans retinoic acid (ATRA) and other medications in the induction phase. Bilateral disc edema was noted during the second consolidation cycle with ATRA. Complete resolution of bilateral disc edema was attained in three weeks' time after discontinuing ATRA.

Developing long bones respond to surrounding tissues by trans-pairing of periosteal osteoclasts and endocortical osteoblasts.

Developing long bones alter their shape while maintaining uniform cortical thickness via coordinated activity of bone-forming osteoblasts and bone-resorbing osteoclasts at periosteal and endosteal surfaces, a process we designate trans-pairing. Two types of trans-pairing shift cortical bone in opposite orientations: peri-forming trans-pairing (peri-t-p) increases bone marrow space and endo-forming trans-pairing (endo-t-p) decreases it, via paired activity of bone resorption and formation across the cortex. Here, we focused on endo-t-p in growing bones. Analysis of endo-t-p activity in the cortex of mouse fibulae revealed osteoclasts under the periosteum compressed by muscles and expression of RANKL in periosteal cells of the cambium layer. Furthermore, mature osteoblasts were localized on the endosteum, while preosteoblasts were at the periosteum and within cortical canals. X-ray tomographic microscopy revealed the presence of cortical canals more closely associated with endo- than with peri-t-p. Sciatic nerve transection followed by muscle atrophy and unloading induced circumferential endo-t-p with concomitant spread of cortical canals. Such canals likely supply the endosteum with preosteoblasts from the periosteum under endo-t-p, allowing bone shape to change in response to mechanical stress or nerve injury.

Five unaddressed questions about cytokinin biosynthesis.

Cytokinins, a class of phytohormones, play crucial roles in regulating plant growth and stress responses through finely tuned feedback loops involving metabolic and signaling cascades. Cytokinin metabolism modulates the abundance of these biologically active molecules. Over the past 25 years, studies have identified key genes involved in cytokinin biosynthesis and inactivation pathways. Nevertheless, several gaps remain in our understanding, particularly regarding the movement of intermediate metabolites between subcellular compartments and the discrepancy between the product of adenosine phosphate-isopentenyltransferase (IPT) and the substrate preferences of subsequent reactions. In addition, recent gene discoveries related to lonely guy (LOG)-independent pathways suggest a spatial extension of cytokinin biosynthesis into the apoplast. Other intriguing issues remain to be addressed, i.e., elucidating the synthetic pathway for cis-zeatin and unraveling the molecular mechanisms governing selective substrate use by the cytokinin biosynthetic enzyme tumor morphology root (Tmr) derived from the phytopathogen Agrobacterium tumefaciens during crown gall formation. Further studies are needed to reveal a fully comprehensive picture of cytokinin metabolism.

FUCA1: An Underexplored p53 Target Gene Linking Glycosylation and Cancer Progression.

Cancer is a difficult-to-cure disease with high worldwide incidence and mortality, in large part due to drug resistance and disease relapse. Glycosylation, which is a common modification of cellular biomolecules, was discovered decades ago and has been of interest in cancer research due to its ability to influence cellular function and to promote carcinogenesis. A variety of glycosylation types and structures regulate the function of biomolecules and are potential targets for investigating and treating cancer. The link between glycosylation and carcinogenesis has been more recently revealed by the role of p53 in energy metabolism, including the p53 target gene alpha-L-fucosidase 1 (FUCA1), which plays an essential role in fucosylation. In this review, we summarize roles of glycan structures and glycosylation-related enzymes to cancer development. The interplay between glycosylation and tumor microenvironmental factors is also discussed, together with involvement of glycosylation in well-characterized cancer-promoting mechanisms, such as the epidermal growth factor receptor (EGFR), phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and p53-mediated pathways. Glycan structures also modulate cell-matrix interactions, cell-cell adhesion as well as cell migration and settlement, dysfunction of which can contribute to cancer. Thus, further investigation of the mechanistic relationships among glycosylation, related enzymes and cancer progression may provide insights into potential novel cancer treatments.

Chemotherapy-free approaches to newly-diagnosed acute promyelocytic leukaemia: is oral-arsenic trioxide/all-trans retinoic acid/ascorbic acid the answer?

INTRODUCTION: Acute promyelocytic leukemia (APL) is a distinct form of acute myeloid leukemia characterized by the presence of t(15;17)(q24;21) and the PML:RARA gene fusion. Frontline use of intravenous arsenic trioxide (i.v.-ATO) and all-trans retinoic acid (ATRA) has vastly improved cure rates in APL. Researchers in Hong Kong invented the oral formulation of ATO (oral-ATO) and have confirmed a bioavailability comparable to i.v.-ATO. A plethora of studies have confirmed the safety and efficacy of oral-ATO-based regimens in the frontline and relapsed setting. AREAS COVERED: Aspects on the development of oral-ATO-based regimens for APL in the frontline and relapsed setting are discussed. The short-term and long-term safety and efficacy of oral-ATO-based regimens are discussed. The frontline use of oral-ATO in combination with ATRA and ascorbic acid (AAA) induction in a 'chemotherapy-free' is highlighted. EXPERT OPINION: Current and ongoing data on the use of oral-ATO-based regimens in APL support the use of oral-ATO as an alternative to i.v.-ATO allowing a more convenient and economical approach to the management of APL.

Enhanced cold plasma hydrogenation with glycerol as hydrogen source for production of trans-fat-free margarine.

The quest for better nutritious foods has encouraged novel scientific investigations to find trans-fat reduction methods. This research proposes an innovative approach for the production of healthier trans-fat-free margarine from palm oil by the use of dielectric barrier discharge (DBD) plasma technology with glycerol serving as the principal source of hydrogen. The effectiveness of DBD plasma in hydrogenating palm olein was investigated. By employing a methodical series of experiments and thorough analytical approaches, examination of the saturated fatty acid conversion experienced its iodine value (IV) reduction from 67.16 ± 0.70 to 31.61 ± 1.10 under the optimal process parameters of 1 L min-1 He flow rate, 35 W plasma discharge power, 10 mm gap size, ambient initial temperature, and 12 h reaction time with solid texture. According to the method for producing trans-fat-free margarine in the absence of a catalyst and H2 gas, the hydrogenation rate of the prepared mixture of palm olein-glycerol was remarkably improved; the trans-fat content in the produced product was zero; the efficacy of incorporating cis- and trans-isomerization was lowered, and the method has a promising industrial application prospect.

High Hepatitis B Prevalence and Vaccination Needs Among Transgender Women and Men Sex Workers in Barcelona, Spain.

Background: Transgender women sex workers (TWSWs) and men sex workers (MSWs) are especially vulnerable to acquiring hepatitis B virus (HBV) infection. We aimed to describe HBV prevalence (hepatitis B surface antigen [HBsAg] and core antibody [HBcAb]) and associated risk factors for HBV exposure (HBcAb), to assess vaccination status and risk factors for no prior vaccination, and to compare HBV prevalence and vaccination status between TWSWs and MSWs. Methods: The SexCohort study was advertised to TWSWs and MSWs through several communication channels. At cohort entry through 2 community-based organizations in Barcelona, the study population was screened for HBV and other sexually transmitted infections, and an epidemiological questionnaire was administered (n = 271). Results: Overall, 93.0% of participants were migrants, mostly from South and Central American countries. HBsAg prevalence was 1.9% (TWSWs, 2.4%; vs MSWs, 0.9%; P = .42), and previous exposure to HBV was 31.8% (TWSWs, 38.5%; vs MSWs, 20.8%; P = .002). Over 5 years of sex work (adjusted odds ratio [aOR], 9.35), prior exposure to Treponema pallidum (aOR, 3.49), and treatment with anxiolytic drugs (aOR, 3.23) were associated with HBV exposure. Overall, 33.7% of participants exhibited immunity from vaccination (TWSWs, 30.8%; vs MSWs, 38.61%; P < .001), while 34.4% were candidates to HBV vaccination (TWSWs, 30.8%; vs MSWs, 40.6%; P < .001). Never having been on pre-exposure prophylaxis for HIV (odds ratio [OR], 4.23) and non-Spanish origin (OR, 5.00) were associated with no prior HBV vaccination. Conclusions: There is a need to reinforce screening and vaccination programs aimed at TWSWs and MSWs as integrated services offered at the community centers commonly accessed by these populations.

Trans-Cervical Approach To The Thoracic Outlet Syndrome.

Thoracic outlet syndrome is caused by compression of the neurovascular structures within the thoracic outlet leading to a collection of symptoms in the upper limb and shoulder. Identification of the causative factor is essential and thorough clinical examination using specific manoeuvres can aid in the diagnosis of this syndrome. Cervical rib is one of the causes for thoracic outlet syndrome and this manuscript will discuss the thoracic outlet syndrome, cervical rib, incidence, clinical presentation, diagnosis and management including surgical approaches with a focus on transcervical approach.

Adaptation and Validation of Voice Handicap Index-Punjabi.

Patients with Voice problems are frequently encountered in clinics. There is no tool available in Punjabi language for evaluation of impact of voice disorder on patient's life. The aim of this study was to adapt Voice Handicap Index in Punjabi language and to obtain validity, reliability and consistency of the developed tool. The study also aims to compare the scores of VHI-Punjabi between patients with voice problems and asymptomatic age-matched controls. The study follows qualitative research design with purposive sampling. The study was conducted at the Audiology and SLP unit of ENT, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab. A total of 200 subjects in the age group of 20-50 years were included, 100 each in study and control group. Combination of reverse translation, committee, and bilingual models were used for development of VHI-Punjabi. The construct validity was very good (r = 0.91). A statistically significant difference (p < 0.001) was obtained between the study group and control group in all the subtest scores and on the total scores of VHI-Punjabi. Statistical significant correlation is found in two administrations of VHI-Punjabi after a gap of 2 weeks in both study group and control group (p < 0.001). To find the internal consistency of VHI-Punjabi, Chronbach alpha was calculated, which came to be 0.97. The internal consistency was high. The results of the present study indicate that VHI-Punjabi is a valid and reliable tool that can be used for evaluation of patients with different types of voice problems.

The efficacy of the novel "wall pierce" technique for common femoral access in endovascular therapy.

Under challenging common femoral artery access scenarios, the "wall PIERCE" technique, which utilizes a larger puncture needle to pierce the vessel wall along the guidewire, facilitates sheath insertion. This method proved successful in two cases without any complications, presenting a valuable addition to strategies for addressing challenging sheath insertion scenarios.

Successful chemical ablation for intraventricular septal ventricular tachycardia-An alternative approach to the septal branch.

Trans-coronary ethanol ablation for ventricular tachycardia originating from the ventricular septum is effective, but there are cases with no septal perforator from left anterior descending artery. CT and angiography can reveal the optimal vessel.

Self-Perceived Reasons for Suicide Attempts in Sexual and Gender Minorities in Canada.

The aim of this study was to examine the self-perceived reasons of suicide attempts among sexual and gender minorities (SGM). We surveyed SGM living in Canada (n = 2778) and respondents who had attempted suicide answered open-ended questions about their perceived reason(s) of their first/only attempt (FOA) and last attempt (LA) (for those who attempted multiple times). Responses were double-coded and categorized as discrete findings. A quarter (25%, n = 695) of the total sample reported a history of suicide attempt, of whom 72% reported multiple attempts. Respondents described a wide variety of reasons for their suicide attempts, with an important number of individuals reporting multiple reasons (corresponding to 47.5% of FOA and 43% of LA). Emotional issues (FOA:42.1%, LA:44.0%) were the most prevalent category of reasons for suicide attempts followed by experience of mental illness (FOA:30.1%, LA:36.1%). Other common reasons included violence (FOA:23.2%, LA:10.2%), interpersonal conflict (FOA:13.4%, LA:6.0%), stress related to life circumstances (FOA:9.5%, LA:16.7%), relationship issues (FOA:7.9%, LA:13.3%), and minority stress related to sexuality (FOA:11.1%, LA:6.2%) and gender identity (FOA:5.0%, LA:6.8%). SGM assessments of the reasons underlying their suicide attempts yielded a variety of factors, many of which were absent from the literature on SGM suicide but amenable to tailored interventions.

Body-Related Existential Dilemmas During Gender Transition: Research in the Italian Context.

The scientific literature shows that gender transition is effective in improving the general well-being of transgender people. However, so far, little attention has been paid to the actual role of the body concerning the existential dilemma that holds the person hostage during transition. This study investigates the relationship between the body-here considered in its concrete, experienced, imagined, and intersubjective dimensions-and gender identity. Twenty-five transgender people who live in Italy were interviewed to identify interpretive repertoires and identity positionings. Four main repertoires and positionings emerged: 1) Interpretative repertoires on the body in transition, where an enduring influence of gender binarism and biological determinants were observed; 2) Expectations regarding medically induced modifications of the body ranging from self-confidence to uncertainty; 3) Positionings toward medically induced bodily modifications, ranging from enthusiasm to resignation; and 4) Inter- and Intrapersonal positionings, where the other than self was found to act as a self-confirming resource or as a constant unpredictable and potentially threatening source of disconfirmation. Practitioners need to develop a stronger awareness of the different dimensions, meanings, and discourses surrounding bodily experience to more effectively intervene in their clinical practice with transgender people.

Xist RNA binds select autosomal genes and depends on Repeat B to regulate their expression.

Xist, a pivotal player in X chromosome inactivation (XCI), has long been perceived as a cis-acting long noncoding RNA that binds exclusively to the inactive X chromosome (Xi). However, Xist's ability to diffuse under select circumstances has also been documented, leading us to suspect that Xist RNA may have targets and functions beyond the Xi. Here, using female mouse embryonic stem cells (ES) and mouse embryonic fibroblasts (MEF) as models, we demonstrate that Xist RNA indeed can localize beyond the Xi. However, its binding is limited to ~100 genes in cells undergoing XCI (ES cells) and in post-XCI cells (MEFs). The target genes are diverse in function but are unified by their active chromatin status. Xist binds discretely to promoters of target genes in neighborhoods relatively depleted for Polycomb marks, contrasting with the broad, Polycomb-enriched domains reported for human XIST RNA. We find that Xist binding is associated with down-modulation of autosomal gene expression. However, unlike on the Xi, Xist binding does not lead to full silencing and also does not spread beyond the target gene. Over-expressing Xist in transgenic ES cells similarly lead to autosomal gene suppression, while deleting Xist's Repeat B motif reduces autosomal binding and perturbs autosomal down-regulation. Furthermore, treating female ES cells with the Xist inhibitor, X1, leads to loss of autosomal suppression. Altogether, our findings reveal Xist targets ~100 genes beyond the Xi, identify Repeat B as a crucial domain for its in-trans function in mice, and indicate that autosomal targeting can be disrupted by the X1 small molecule inhibitor.

Human esophageal cancer stem-like cells escape the cytotoxicity of natural killer cells via down-regulation of ULBP-1.

BACKGROUND: Cancer stem-like cells (CSCs) play an important role in initiation and progression of aggressive cancers, including esophageal cancer. Natural killer (NK) cells are key effector lymphocytes of innate immunity that directly attack a wide variety of cancer cells. NK cell-based therapy may provide a new treatment option for targeting CSCs. In this study, we aimed to investigate the sensitivity of human esophageal CSCs to NK cell-mediated cytotoxicity. METHODS: CSCs were enriched from human esophageal squamous cell carcinoma cell lines via sphere formation culture. Human NK cells were selectively expanded from the peripheral blood of healthy donors. qRT-PCR, flow cytometry and ELISA assays were performed to examine RNA expression and protein levels, respectively. CFSE-labeled target cells were co-cultured with human activated NK cells to detect the cytotoxicity of NK cells by flow cytometry. RESULTS: We observed that esophageal CSCs were more resistant to NK cell-mediated cytotoxicity compared with adherent counterparts. Consistently, esophageal CSCs showed down-regulated expression of ULBP-1, a ligand for NK cells stimulatory receptor NKG2D. Knockdown of ULBP-1 resulted in significant inhibition of NK cell cytotoxicity against esophageal CSCs, whereas ULBP-1 overexpression led to the opposite effect. Finally, the pro-differentiation agent all-trans retinoic acid was found to enhance the sensitivity of esophageal CSCs to NK cell cytotoxicity. CONCLUSIONS: This study reveals that esophageal CSCs are more resistant to NK cells through down-regulation of ULBP-1 and provides a promising approach to promote the activity of NK cells targeting esophageal CSCs.

Pituitary lymphoma appearing 9 years after pituitary adenoma resection.

Background: Pituitary lymphomas (PLs) are very rare, accounting for <0.1% of all intracranial tumors. Of which, PL that is associated with PL is even rarer. Here, we describe a case of PL of a 51-year-old woman that appeared 9 years after pituitary adenoma resection. Case Description: A 51-year-old woman presented with visual disturbance. She had a history of pituitary adenoma resected through endoscopic trans-sphenoidal surgery (eTSS) 9 years before. Although her previous annual follow-up did not show any signs of recurrence, she noticed visual disturbance. One month later, her visual acuity rapidly worsened with headache and fatigue, being referred to our hospital. On examination, she had bilateral quadrantanopia. Her laboratory data showed slightly increased prolactin levels. Magnetic resonance images showed a mass in the sella with suprasellar extension, so she underwent eTSS. The tumor had a fibrous, hard part and a soft gray part, and it was mostly resected. Visual symptoms improved transiently, but ophthalmoplegia appeared 2 weeks after surgery, indicating intrathecal dissemination. Histological analysis confirmed the diagnosis of T-lymphoblastic lymphoma. Positron emission tomography showed tracer accumulation at the pancreas, confirmed as lymphoma through biopsy. However, we could not determine which site of lymphoma was the primary site. She underwent chemotherapy, including cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, and methotrexate. The patient died despite several months of treatment. Conclusion: Recurrence of pituitary adenoma cannot be carelessly assumed from a pituitary growing mass after pituitary adenoma resection. PLs have poor prognosis due to their aggressive character. Immediate biopsy and confirmation of the diagnosis are necessary for the treatment of pituitary masses with aggressive features.

A Rare Case of Early Gastric Cancer With Rapid Bone Involvement.

Gastric cancers rarely metastasize to the bones. If they do, they have a very poor prognosis. We here present a case study of a 56-year-old man who, within a year, rapidly declined and died. He was first revealed to have an erosion found on an esophageal gastroduodenoscopy (EGD), which was later proven to be a poorly differentiated gastric adenocarcinoma. He then proceeded to have a thoracic trans-hiatal esophagogastrostomy with gastric pull-up to resect this cancer. At this point in time, the review of systems and CT scans of the abdomen and pelvis were negative. A few months later, he started having back pain and was diagnosed with metastatic disease of the bones through a CT scan. Although detecting gastric cancer at an early stage is rare, it is shown to have a better prognosis. It is, therefore, very important to reflect on the possibility of engaging in earlier screening to detect gastric cancers at an earlier stage to minimize the risk of invasions of other organs, especially for those who have other risk factors such as obesity and tobacco use. We believe it is prudent to ensure close follow-up with any patient with early gastric cancer to potentially detect recurrence or metastasis in a timely fashion.