RN7SL1 may be translated under oncogenic conditions.

RN7SL1 (RNA component of signal recognition particle 7SL1), a component of the signal recognition particle, is a non-coding RNA possessing a small ORF (smORF). However, whether it is translated into peptides is unknown. Here, we generated the RN7SL1-Green Fluorescent Protein (GFP) gene, in which the smORF of RN7SL1 was replaced by GFP, introduced it into 293T cells, and observed cells emitting GFP fluorescence. Furthermore, RNA-seq of GFP-positive cells revealed that they were in an oncogenic state, suggesting that RN7SL1 smORF may be translated under special conditions.

Fat and proteolysis due to methionine, tryptophan, and niacin deficiency leads to alterations in gut microbiota and immune modulation in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is one of the intractable diseases. Nutritional components associated with IBD have been identified, and it is known that excessive methionine intake exacerbates inflammation, and that tryptophan metabolism is involved in inflammation. Analysis of the gut microbiota has also progressed, where Lactobacillus regulate immune cells in the intestine and suppress inflammation. However, whether the methionine and tryptophan metabolic pathways affect the growth of intestinal Lactobacillus is unknown. Here we show how transient methionine, tryptophan, and niacin deficiency affects the host and gut microbiota in mouse models of colitis (induced by dextran sodium sulfate) fed a methionine-deficient diet (1K), tryptophan and niacin-deficient diet (2K), or methionine, tryptophan, and niacin-deficient diet (3K). These diets induced body weight decrease and 16S rRNA analysis of mouse feces revealed the alterations in the gut microbiota, leading to a dramatic increase in the proportion of Lactobacillus in mice. Intestinal RNA sequencing data confirmed that the expression of several serine proteases and fat-metabolizing enzymes were elevated in mice fed with methionine, tryptophan, and niacin (MTN) deficient diet. In addition, one-carbon metabolism and peroxisome proliferator-activated receptor (PPAR) pathway activation were also induced with MTN deficiency. Furthermore, changes in the expression of various immune-related cytokines were observed. These results indicate that methionine, tryptophan, and niacin metabolisms are important for the composition of intestinal bacteria and host immunity. Taken together, MTN deficiencies may serve as a Great Reset of gut microbiota and host gene expression to return to good health.

RNA methylation in inflammatory bowel disease.

RNA modifications, including the renowned m6A, have recently garnered significant attention. This chemical alteration, present in mRNA, exerts a profound influence on protein expression levels by affecting splicing, nuclear export, stability, translation, and other critical processes. Although the role of RNA methylation in the pathogenesis and progression of IBD and colorectal cancer has been reported, many aspects remain unresolved. In this comprehensive review, we present recent studies on RNA methylation in IBD and colorectal cancer, with a particular focus on m6A and its regulators. We highlight the pivotal role of m6A in the pathogenesis of IBD and colorectal cancer and explore the potential applications of m6A modifications in the diagnosis and treatment of these diseases.

High N6-methyladenosine-activated TCEAL8 mRNA is a novel pancreatic cancer marker.

N6-methyladenosine (m6A) is an RNA modification involved in RNA processing and widely found in transcripts. In cancer cells, m6A is upregulated, contributing to their malignant transformation. In this study, we analyzed gene expression and m6A modification in cancer tissues, ducts, and acinar cells derived from pancreatic cancer patients using MeRIP-seq. We found that dozens of RNAs highly modified by m6A were detected in cancer tissues compared with ducts and acinar cells. Among them, the m6A-activated mRNA TCEAL8 was observed, for the first time, as a potential marker gene in pancreatic cancer. Spatially resolved transcriptomic analysis showed that TCEAL8 was highly expressed in specific cells, and activation of cancer-related signaling pathways was observed relative to TCEAL8-negative cells. Furthermore, among TCEAL8-positive cells, the cells expressing the m6A-modifying enzyme gene METTL3 showed co-activation of Notch and mTOR signaling, also known to be involved in cancer metastasis. Overall, these results suggest that m6A-activated TCEAL8 is a novel marker gene involved in the malignant transformation of pancreatic cancer.

Relationship between the elasticity of the forearm flexor-pronator muscles and elbow valgus torque in young baseball pitchers: a descriptive laboratory study.

BACKGROUND: The forearm flexor-pronator muscles act as a dynamic elbow stabilizer against elbow valgus load during baseball pitching. The elasticity of these muscles increases with pitching. However, it is unclear whether increased muscle elasticity is associated with greater elbow valgus torque during pitching. This study aimed to determine the relationship between the elasticity of the forearm flexor-pronator muscles and elbow valgus torque during pitching in young baseball pitchers. METHODS: We recruited 124 young baseball pitchers aged 9 to 12 years. The exclusion criteria included current pain with pitching, history of surgery on the tested extremity, or injuries on the tested extremity within the past 12 months. Before the examination, participants completed a questionnaire about their age, height, weight, dominant arm and practice time per week. The strain ratios of flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), and pronator teres as the index of muscle elasticity were measured using ultrasound strain elastography. Participants pitched three fastballs at a distance of 52 ft 6 in (16 m) with maximum effort while wearing a sensor sleeve that recorded the elbow valgus torque. A multiple linear regression analysis was conducted to examine the association between muscle elasticity and elbow valgus torque, adjusting for age, height, weight, and practice time. RESULTS: The final analysis included 107 pitchers. After adjusting for covariates, increased strain ratio of the FCU was significantly associated with greater elbow valgus torque (coefficients = 0.038, 95% confidence interval [CI], 0.016-0.059, P<.001). Similarly, increased strain ratio of the FDS was significantly associated with greater elbow valgus torque (coefficients = 0.027, 95% CI, 0.013-0.042, P<.001). CONCLUSION: The high elasticities of the FCU and FDS were associated with greater elbow valgus torque during pitching in young baseball pitchers. The high elasticity of these muscles is a protective response and may be necessary for young baseball pitchers with greater elbow valgus torque during pitching. Among young baseball pitchers with greater elbow valgus torque, those who are unable to produce the higher elasticities of these muscles could have greater elbow valgus load during pitching and be at a higher risk for elbow injuries. The measurement of the elasticities of the FCU and FDS may be useful for identifying young baseball pitchers at risk of sustaining elbow injuries.

Multifaced roles of desmoplastic reaction and fibrosis in pancreatic cancer progression: Current understanding and future directions.

Desmoplastic reaction is a fibrosis reaction that is characterized by a large amount of dense extracellular matrix (ECM) and dense fibrous stroma. Fibrotic stroma around the tumor has several different components, including myofibroblasts, collagen, and other ECM molecules. This stromal reaction is a natural response to the tissue injury process, and fibrosis formation is a key factor in pancreatic cancer development. The fibrotic stroma of pancreatic cancer is associated with tumor progression, metastasis, and poor prognosis. Reportedly, multiple processes are involved in fibrosis, which is largely associated with the upregulation of various cytokines, chemokines, matrix metalloproteinases, and other growth factors that promote tumor growth and metastasis. Fibrosis is also associated with immunosuppressive cell recruitment, such as regulatory T cells (Tregs) with suppressing function to antitumor immunity. Further, dense fibrosis restricts the flow of nutrients and oxygen to the tumor cells, which can contribute to drug resistance. Furthermore, the dense collagen matrix can act as a physical barrier to block the entry of drugs into the tumor, thereby further contributing to drug resistance. Thus, understanding the mechanism of desmoplastic reaction and fibrosis in pancreatic cancer will open an avenue to innovative medicine and improve the prognosis of patients suffering from this disease.

Increased Medial Elbow Torque Is Associated With Ball Velocity Rather Than a History of Medial Elbow Injuries in Youth Baseball Pitchers.

PURPOSE: This study compared medial elbow torque in youth baseball pitchers with and without a history of medial elbow injuries to determine the relationship between medial elbow torque during pitching and having a history of medial elbow injuries. METHODS: We recruited 171 youth baseball pitchers aged 9 to 12 years old. The exclusion criteria included current pain with pitching, history of surgery on the tested extremity, or osteochondritis dissecans of the humeral capitellum. The participants were grouped into 3 groups: injury <1-year, injury >1-year, and control, based on ultrasonographic abnormalities of the elbow and the presence of elbow pain. Pitchers pitched 3 fastballs while wearing a sensor sleeve that recorded the medial elbow torque, arm speed, and shoulder rotation. Ball velocity was measured using a radar gun. RESULTS: The final analysis included 164 pitchers. Thirty were assigned to the injury <1-year group, 34 to the injury >1-year group, and 100 to the control group. The medial elbow torque was significantly greater in the injury <1-year group compared with the control group (18.6 ± 3.6 Nm vs 16.2 ± 4.8 Nm, P = .023). A multiple regression analysis revealed that ball velocity (B = 0.282, P < .001) and body weight (B = -0.224, P < .001) were significantly associated with medial elbow torque, but not with the history of medial elbow injuries. CONCLUSIONS: Increased medial elbow torque was associated with greater ball velocity regardless of the history of medial elbow injuries. Youth baseball pitchers with a history of medial elbow injuries within one year had greater medial elbow torque during pitching; however, having a history of medial elbow injuries was not an independent factor in increasing medial elbow torque. Limiting the ball velocity can reduce medial elbow torque and may prevent elbow injuries in youth baseball pitchers. LEVEL OF EVIDENCE: Level II, prospective comparative prognostic investigation with the patients enrolled at different time point.

Perioperative fluid management influences complication rates and length of hospital stay in the enhanced recovery after surgery (ERAS) protocol for patients with colorectal cancer.

PURPOSE: To evaluate the efficacy and safety of the enhanced recovery after surgery (ERAS) protocol and quantify the impact of each ERAS item on postoperative outcomes. METHODS: We used a generalized linear model to compare 289 colorectal cancer patients treated with the ERAS protocol between June, 2015 and April, 2021, with 99 colorectal cancer patients treated with the conventional colorectal surgery pathway between April, 2014 and June, 2015. RESULTS: The median length of hospital stay (LOHS) was significantly shorter in the ERAS group, at 9 days (range 3-104 days) vs. 14 days (range 4-44 days) (p < 0.001), but the complication rates (Clavien-Dindo grade 2 or more) were similar (16.6% vs. 22.2%; p = 0.227). However, in the ERAS group, the higher the compliance with ERAS items, the lower the complication rate and LOHS (both p < 0.001). Multiple regression analysis demonstrated that "Discontinuation of continuous intravenous infusion on POD1" and "Avoidance of fluid overload" were significantly associated with the LOHS (p < 0.001 and p = 0.008). CONCLUSION: The ERAS protocol is safe and effective for elective colorectal cancer surgery, and compliance with the ERAS protocol contributes to shorter LOHS and fewer complications. Items related to perioperative fluid management had a crucial impact on these outcomes.

[A Case of Conversion Surgery for Gallbladder Cancer with Para-Aortic Lymph Node Metastasis].

The study presents the case of a 71-year-old woman who visited a nearby hospital for epigastric pain and weight loss. A CT scan showed a mass in the gallbladder, and the CEA level was high, so she was referred to our hospital for further investigation. Abdominal US, CT, and MRI suggested gallbladder cancer with para-aortic metastasis, and the histological findings on the EUS-FNA confirmed the diagnosis. Since surgical resection was not indicated, chemotherapy was performed(gemcitabine plus cisplatin). After 10 courses of chemotherapy, CT and MRI showed downsizing of para-aortic lymph nodes, and no accumulation of FDG was found on FDG-PET. Confirming the downstaging of cancer, conversion surgery, comprising an extended cholecystectomy and a lymph node resection, was performed. The pathological diagnosis showed no lymph node metastasis. No recurrence was observed after 12 months of surgery. Initially, unresectable gallbladder cancer with para-aortic lymph node metastasis was indicated to be compatible with preoperative chemotherapy and conversion surgery.

[A Case of Cardiac Tamponade during Multimodal Treatment for Mediastinal Lymph Node Metastasis of Gastric Cancer].

A 52-year-old man underwent total gastrectomy for gastric cancer and chemoradiotherapy for thoracic paraaortic lymph node metastasis. He also underwent esophageal stent implantation for stenosis. He was admitted to our hospital with fever and breathing difficulty and was diagnosed with infectious pericarditis. He showed symptoms of shock due to cardiac tamponade. After pericardial drainage, his vital signs improved. When signs of infection are detected in patients with a history of chemoradiotherapy or stent implantation, we should consider infectious pericarditis due to esophageal pericardial fistula and apply immediate drainage of cardiac tamponade.

High Thoracic Kyphosis and Backward Trunk Inclination Angles in the Single-Leg Standing Position Associate With Medial Elbow Injuries in Youth Baseball Players: A Cross-Sectional Study.

CONTEXT: Baseball pitching is a coordinated movement involving the spine. A previous study indicated that increased thoracic kyphosis angle in a standing position was a risk factor for medial elbow injuries in youth baseball players. However, spinal alignments in single-leg standing and their relationships with medial elbow injuries, scapular alignment, or hip joint range of motion are unclear. OBJECTIVE: To examine the difference in spinal alignment between standing and single-leg standing positions in youth baseball players and analyze their relationship with elbow injuries, scapular alignment, or hip joint range of motion. DESIGN: Cross-sectional study. SETTING: University laboratory. PARTICIPANTS: There were 51 youth baseball players with medial epicondylar fragmentation (medial elbow injury group) and 102 healthy youth baseball players (control group). MAIN OUTCOME MEASURES: Thoracic kyphosis, lumbar lordosis, and trunk inclination angles during standing and single-leg standing, forward scapular posture, and hip joint range of motion. RESULTS: In the single-leg standing position, the thoracic kyphosis and backward trunk inclination angles were significantly higher in the medial elbow injury group than in the control group (P = .016 and P = .046, respectively). In the standing position, no significant difference was observed between both groups. The thoracic kyphosis angle in single-leg standing was positively correlated with the bilateral forward scapular posture in the medial elbow injury (P = .008 and P < .001 on the throwing and nonthrowing sides, respectively) and control (P = .010 and P = .032 on the throwing and nonthrowing sides, respectively) groups. CONCLUSIONS: High thoracic kyphosis and backward trunk inclination angles are characteristics during single-leg standing in youth baseball players with medial elbow injuries. Spinal alignment measurement in single-leg standing may be useful for identifying youth baseball players who are at risk for sustaining medial elbow injury.

Hyperechoic and Low Morphological Changes in the Prefemoral Fat Pad in Individuals with Knee Osteoarthritis Based on Ultrasonographic Findings.

BACKGROUND: To clarify the changes in the echo intensity (EI) in the prefemoral fat pad (PFP) and identify the relationship between the PFP and clinical features of knee osteoarthritis (OA). METHODS: Twenty-six women with knee OA (mean age: 76 years) and 17 healthy women (mean age: 73 years) were enrolled. The Kellgren and Lawrence grading scale was used for the radiographic evaluation of knee OA. The EI of the PFP was measured as grayscale values. The change ratio of the anteroposterior PFP length during quadriceps contraction was measured. Knee range of motion and pain (100-mm visual analog scale) were evaluated. RESULTS: The EI was significantly higher in the OA group than in the healthy group (P < 0.001). The change ratio of the PFP in the OA group was significantly lower than that in the healthy group (P < 0.001). The ranges of knee flexion and extension were correlated with the EI of the PFP (both P < 0.01) and the change ratio of the PFP (both P < 0.01). There was no significant correlation observed with knee pain. CONCLUSION: Hyperechoic changes and a decreased change ratio of the PFP were observed in the patients with knee OA. High EI and decreased morphological PFP changes were associated with decreased ranges of motion.

[Laparoscopic Tumor Resection for Retroperitoneal Leiomyosarcoma-A Case Report].

A 59-year-old man visited our department because of cholecystectomy. Preoperative CT revealed a tumor shadow measuring 50 mm in front of the right iliopsoas muscle. MRI showed a low signal intensity on T1-weighted images and a slightly high signal intensity on the T2-weighted image. PET-CT showed accumulation of FDG(SUVmax 5.39)in the tumor but no other abnormal accumulations. We performed tumor resection for diagnostic purposes because malignancy could not be ruled out owing to the large size of the mass. Intraoperative findings showed a well-circumscribed margin of the tumor without invasion to other tissues. The retroperitoneum was incised circumferentially along the tumor under laparoscopic guidance, and the tumor was resected. Histopathological and immunostaining findings were consistent with leiomyosarcoma. In laparoscopic surgery, the surgical margin is observed in detail through the magnifying effect. Therefore, laparoscopic surgery can be a surgical option for tumors that may be completely excised based on preoperative findings.

Ultrasonographic Morphological Changes in the Prefemoral Fat Pad Associated with Knee Osteoarthritis.

BACKGROUND: In normal knees, quadriceps contraction changes the shape of the prefemoral fat pad (PFP). However, in persons with knee osteoarthritis (OA), the functional or morphological changes of the PFP are unclear. This study aimed to clarify the morphological changes in the PFP in individuals with knee OA through ultrasonography. MATERIALS AND METHODS: Participants were divided into the OA (36 knees; mean age, 74 years), elderly (31 knees; mean age, 70 years), and young (26 knees; mean age, 21 years) groups. The anteroposterior (AP) length of the PFP before and during isometric quadriceps contraction at 0°, 30°, 60°, and 90° knee flexion was measured ultrasonographically. The difference between the maximum and minimum length values, change in length, was also measured. These parameters were compared among the three groups. In the OA group, correlations between the parameters and clinical features (knee pain; visual analog scale, knee range of motion [ROM], Kellgren and Lawrence (K/L) grade, and intercondylar distance) were examined by Spearman and Pearson's correlation coefficient tests. RESULTS: The AP lengths of the PFP before contraction were significantly lower in the OA group than in elderly group and young group at 30° (6.9 ± 2.5 vs. 12.0 ± 3.6 or 11.1 ± 2.7 mm, respectively; in order P = 0.014, P = 0.006) and 60° (6.5 ± 2.0 vs. 9.7 ± 2.5 or 9.1 ± 2.7 mm, respectively; both P < 0.001). The AP lengths of the PFP during contraction were significantly lower in the OA group than in elderly group and young group at 0° (6.7 ± 2.3 vs. 8.8 ± 3.7 or 9.1 ± 1.6 mm, respectively; both P < 0.001), 30° (7.9 ± 2.6 vs. 12.9 ± 3.7 or 13.0 ± 2.6 mm, respectively; both P < 0.001), and 60° (7.1 ± 2.5 vs. 13.5 ± 2.6 or 13.6 ± 3.0 mm, respectively; both P < 0.001). The change in length before maximum isometric quadriceps contraction was significantly lower in the knee OA group than in both elderly and young groups (3.3 ± 1.9 vs. 8.4 ± 2.5 or 6.8 ± 3.0 mm, respectively; both P < 0.001). The change in length during contraction was also significantly lower in the knee OA group than in both the elderly and young groups (3.9 ± 2.3 vs. 8.7 ± 2.3 or 8.9 ± 2.0 mm, respectively; both P < 0.001). In the OA group, change in length during contraction was significantly associated with knee pain (r = -0.476, P = 0.007), knee ROM (r = 0.388, P = 0.019), and Kellgren and Lawrence grade (r = -0.357, P = 0.045). CONCLUSIONS: In knee OA, movement of PFP was decreased more than healthy participants. In the knee OA group, the decrease of the morphological change of the PFP showed the relationship between VAS score, knee extension ROM, intercondylar distance (ICD), and K/L grade. An evaluation to the PFP may be required in individuals with knee OA.

Spatiotemporal characteristics of surround suppression in primary visual cortex and lateral geniculate nucleus of the cat.

In the primary visual cortex (V1), a neuronal response to stimulation of the classical receptive field (CRF) is predominantly suppressed by a stimulus presented outside the CRF (extraclassical receptive field, ECRF), a phenomenon referred to as ECRF suppression. To elucidate the neuronal mechanisms and origin of ECRF suppression in V1 of anesthetized cats, we examined the temporal properties of the spatial extent and orientation specificity of ECRF suppression in V1 and the lateral geniculate nucleus (LGN), using stationary-flashed sinusoidal grating. In V1, we found three components of ECRF suppression: (1) local and fast, (2) global and fast, and (3) global and late. The local and fast component, which resulted from within 2° of the boundary of the CRF, started no more than 10 ms after the onset of the CRF response and exhibited low specificity for the orientation of the ECRF stimulus. These spatiotemporal properties corresponded to those of geniculate ECRF suppression, suggesting that the local and fast component of V1 is inherited from the LGN. In contrast, the two global components showed rather large spatial extents ∼5° from the CRF boundary and high specificity for orientation, suggesting that their possible origin is the cortex, not the LGN. Correspondingly, the local component was observed in all neurons of the thalamocortical recipient layer, while the global component was biased toward other layers. Therefore, we conclude that both subcortical and cortical mechanisms with different spatiotemporal properties are involved in ECRF suppression.

Spike synchronization in cat primary visual cortex depends on similarity of surround-suppression magnitude.

In the primary visual cortex (V1), the spike synchronization seen in neuron pairs with non-overlapping receptive fields can be explained by similarities in their preferred orientation (PO). However, this is not true for pairs with overlapping receptive fields, as they can still exhibit spike synchronization even if their POs are only weakly correlated. Here, we investigated the relationship between spike synchronization and suppressive modulation derived from classical receptive-field surround (surround suppression). We found that layer 4 and layer 2/3 pairs exhibited mainly asymmetric spike synchronization that had non-zero time-lags and was dependent on both the similarity of the PO and the strength of surround suppression. In contrast, layer 2/3 and layer 2/3 pairs showed mainly symmetric spike synchronization that had zero time-lag and was dependent on the similarity of the strength of surround suppression but not on the similarity in POs. From these results, we propose that in cat V1 there exists a functional network that mainly depends on the similarity in surround suppression, and that in layer 2/3 neurons the network maintains surround suppression that is primarily inherited from layer 4 neurons.

Relative spatial frequency tuning and its contrast dependency in human perception.

Several physiological studies in cats and monkeys have reported that the spatial frequency (SF) tuning of visual neurons varies depending on the luminance contrast and size of stimulus. However, comparatively little is known about the effect of changing the stimulus contrast and size on SF tuning in human perception. In the present study, we investigated the effects of stimulus size and luminance contrast on human SF tuning using the subspace-reverse-correlation method. Measuring SF tunings at six different stimulus sizes and three different luminance contrast conditions (90%, 10%, and 1%), we found that human perception exhibits significant stimulus-size-dependent SF tunings. At 90% and 10% contrast, participants exhibited relative SF tuning (cycles/image) rather than absolute SF tuning (cycles/°) at response peak latency. On the other hand, at 1% contrast, the magnitude of the size-dependent-peak SF shift was too small for strictly relative SF tuning. These results show that human SF tuning is not fixed, but varies depending on the stimulus size and contrast. This dependency may contribute to size-invariant object recognition within an appropriate contrast rage.

Revealing neuropilin expression patterns in pancreatic cancer: From single­cell to therapeutic opportunities (Review).

Pancreatic cancer, one of the most fatal types of human cancers, includes several non-epithelial and stromal components, such as activated fibroblasts, vascular cells, neural cells and immune cells, that are involved in different cancers. Vascular endothelial cell growth factor 165 receptors 1 [neuropilin-1 (NRP-1)] and 2 (NRP-2) play a role in the biological behaviors of pancreatic cancer and may appear as potential therapeutic targets. The NRP family of proteins serve as co-receptors for vascular endothelial growth factor, transforming growth factor ß, hepatocyte growth factor, fibroblast growth factor, semaphorin 3, epidermal growth factor, insulin-like growth factor and platelet-derived growth factor. Investigations of mechanisms that involve the NRP family of proteins may help develop novel approaches for overcoming therapy resistance in pancreatic cancer. The present review aimed to provide an in-depth exploration of the multifaceted roles of the NRP family of proteins in pancreatic cancer, including recent findings from single-cell analysis conducted within the context of pancreatic adenocarcinoma, which revealed the intricate involvement of NRP proteins at the cellular level. Through these efforts, the present study endeavored to further reveal their relationships with different biological processes and their potential as therapeutic targets in various treatment modalities, offering novel perspectives and directions for the treatment of pancreatic cancer.

Tissue-Resident Memory T Cells in Gastrointestinal Cancers: Prognostic Significance and Therapeutic Implications.

Gastrointestinal cancers, which include a variety of esophageal and colorectal malignancies, present a global health challenge and require effective treatment strategies. In the evolving field of cancer immunotherapy, tissue-resident memory T cells (Trm cells) have emerged as important players in the immune response within nonlymphoid tissues. In this review, we summarize the characteristics and functions of Trm cells and discuss their profound implications for patient outcomes in gastrointestinal cancers. Positioned strategically in peripheral tissues, Trm cells have functions beyond immune surveillance, affecting tumor progression, prognosis, and response to immunotherapy. Studies indicate that Trm cells are prognostic markers and correlate positively with enhanced survival. Their presence in the tumor microenvironment has sparked interest in their therapeutic potential, particularly with respect to immune checkpoint inhibitors, which may improve cancer treatment. Understanding how Trm cells work will not only help to prevent cancer spread through effective treatment but will also contribute to disease prevention at early stages as well as vaccine development. The role of Trm cells goes beyond just cancer, and they have potential applications in infectious and autoimmune diseases. This review provides a thorough analysis of Trm cells in gastrointestinal cancers, which may lead to personalized and effective cancer therapies.

Significance of signal recognition particle 9 nuclear translocation: Implications for pancreatic cancer prognosis and functionality.

Signal recognition particles (SRPs) are essential for regulating intracellular protein transport and secretion. Patients with tumors with high SRP9 expression tend to have a poorer overall survival. However, to the best of our knowledge, no reports have described the relationship between SRP9 localization and prognosis in pancreatic cancer. Thus, the present study aimed to investigate this relationship. Immunohistochemical staining for SRP9 using excised specimens from pancreatic cancer surgery cases without preoperative chemotherapy or radiotherapy showed that SRP9 was preferentially expressed in the nucleus of the cancerous regions in some cases, which was hardly detected in other cases, indicating that SRP9 was transported to the nucleus in the former cases. To compare the prognosis of patients with SRP9 nuclear translocation, patients were divided into two groups: Those with a nuclear translocation rate of >50% and those with a nuclear translocation rate of ≤50%. The nuclear translocation rate of >50% group had a significantly better recurrence­free survival than the nuclear translocation rate of ≤50% group (P=0.037). Subsequent in vitro experiments were conducted; notably, the nuclear translocation rate of SRP9 was reduced under amino acid­deficient conditions, suggesting that multiple factors are involved in this phenomenon. To further study the function of SRP9 nuclear translocation, in vitro experiments were performed by introducing SRP9 splicing variants (v1 and v2) and their deletion mutants lacking C­terminal regions into MiaPaCa pancreatic cancer cells. The results demonstrated that both splicing variants showed nuclear translocation regardless of the C­terminal deletions, suggesting the role of the N­terminal regions. Given that SRP9 is an RNA­binding protein, the study of RNA immunoprecipitation revealed that signaling pathways involved in cancer progression and protein translation were downregulated in nuclear­translocated v1 and v2. Undoubtedly, further studies of the nuclear translocation of SRP9 will open an avenue to optimize the precise evaluation and therapeutic control of pancreatic cancer.