Search

Treatment of pancreatic cancer by inhibiting the aberrant activation of the survival signaling pathways has received considerable attention. We investigated the probable action of DHA on the suppression of cell proliferation in human pancreatic ductal adenocarcinoma (PDAC) cells. Our results demonstrated that DHA dose-dependently inhibited cell proliferation through an induction of cell cycle arrest in human PDAC cells. DHA suppressed the expression of phosphorylated-Rb (p-Rb), cyclin D1, cyclin E, cyclin A, E2F1 and c-Myc proteins. Blocking the activation of STAT3 signaling pathway led to an inactivation of CAMKII and increased phosphorylation of c-Myc (T58) protein accompanied with decreased expression of c-Myc protein. Treatment of DHA effectively inhibited cell survival through decreased phosphorylation levels of EGFR, STAT3 and CAMKII proteins. The mechanisms of action were associated with increased phosphorylation levels of c-Myc (T58) and instability of c-Myc proteins. DHA inhibited cell survival through an increased GSSG/GSH ratio and oxidative stress level in HPAF-II cells. DHA induced cell apoptosis through increased expression of Bax, c-caspase 3 and c-PARP proteins in HPAF-II cells. Moreover, treatment of DHA significantly inhibited nucleotide synthesis. In conclusion, DHA might significantly suppress the proliferation of PDAC cells and therefore have potential as an anti-cancer therapeutic agent.

Author(s): Takashi Saito [1, 2]; Nobuhisa Iwata (corresponding author) [1, 2]; Satoshi Tsubuki [1]; Yoshie Takaki [1]; Jiro Takano [1]; Shu-Ming Huang [1]; Takahiro Suemoto [1]; Makoto Higuchi [1]; Takaomi [...]

Abstract Background Calpastatin is an endogenous inhibitor of calpain, intracellular calcium-activated protease. It has been suggested to be involved in molecular mechanisms of long-term plasticity and excitotoxic pathways. However, functions of calpastatin in vivo are still largely unknown. To examine the physiological roles of calpastatin, we subjected calpastatin-knockout mice to a comprehensive behavioral test battery. Results Calpastatin-knockout mice showed decreased locomotor activity under stressful environments, and decreased acoustic startle response, but we observed no significant change in hippocampus-dependent memory function. Conclusion These results suggest that calpastatin is likely to be more closely associated with affective rather than cognitive aspects of brain function.

Microbes may play a substantial role in the weathering and alteration of minerals. However, not enough concerns have been realized about the complexity of microbe-mineral interactions. The present work reports the interactions between fungi and minerals with emphasis on the role of silicate minerals as the metal donor for the precipitation of secondary mineral. Herein, two magnesium-bearing silicate minerals with different structures, forsterite and talc, were added to the submerged cultures ofAspergillus niger(A. niger). It is shown that forsterite exhibits a better solubilization effect than talc, and the secondary mineral glushinskite only precipitates in the presence of forsterite substrates. Oxalic acid excreted byA. nigerplays a key role in the biological leaching and mineralization processes. Moreover, the forsterite particles with certain size added to the cultures tend to inhibit the aggregation of fungal biomass, and therefore affect the morphology ofA. nigeraggregates in the submerged culture. With varying forsterite particle size, distinct fungal morphological forms including mycelial pellets and freely dispersed hyphae can be formed, which have a direct impact on fungal metabolism and ultimately result in varied crystallization habits of the neo-minerals. Particularly in the culture with −40/+60 mesh forsterite particles, the mineralized glushinskite mainly exhibit tubular forms; whereas when forsterite particles were at −100/+120 mesh or −200 mesh, pyramidal prisms are obtained. We show that the environmental factors such as the particle size of mineral substrate could influence the fungal morphology and metabolic activities, thereby leading to different morphological neo-minerals. The dependence of biomineral morphology on the environmental factors can open up a novel avenue to understanding the microorganism-environment interactions. [ABSTRACT FROM AUTHOR]

Expression of somatostatin in the brain declines during aging in various mammals including apes and humans. A prominent decrease in this neuropeptide also represents a pathological characteristic of Alzheimer disease. Using in vitro and in vivo paradigms, we show that somatostatin regulates the metabolism of amyloidßpeptide (Aß), the primary pathogenic agent of Alzheimer disease, in the brain through modulating proteolytic degradation catalyzed by neprilysin. Among various effector candidates, only somatostatin upregulated neprilysin activity in primary cortical neurons. A genetic deficiency of somatostatin altered hippocampal neprilysin activity and localization, and increased the quantity of a hydrophobic 42-mer form of Aß, Aß42, in a manner similar to presenilin gene mutations that cause familial Alzheimer disease. These results indicate that the aging-induced downregulation of somatostatin expression may be a trigger for Aßaccumulation leading to late-onset sporadic Alzheimer disease, and suggest that somatostatin receptors may be pharmacological-target candidates for prevention and treatment of Alzheimer disease. [ABSTRACT FROM AUTHOR]

Abstract The depressant action of adenosine on acetylcholine release at frog motor nerve terminals was studied by intracellular recording and Ca2+ -imaging techniques. Adenosine (200 µm) quickly and reversibly decreased the amplitude and quantal content of end-plate potentials (EPPs) with no change in quantal size in a low-Ca2+ , high-Mg2+ solution, and EPP amplitude in normal Ringer containing d-tubocurarine. Likewise, adenosine (200 µm) reduced miniature EPP (MEPP) frequency, but not amplitude, in a high-K+ (6 mm) solution. Adenosine (40–200 µm), however, did not affect single or repetitive impulse(s)-induced rises in Ca2+ in the nerve terminals or its basal level. Adenosine (100–200 µm) reduced the Ca2+ -independent enhancement of MEPP frequency caused by hypertonicity. EPPs induced by tetanic stimulation (33 Hz) in Ringer with d-tubocurarine initially increased in amplitude within 10 stimuli and then declined to the minimum. Adenosine (200 µm) decreased EPP amplitude in the initial phase of the tetanus, but enhanced it in the middle phase, thus prolonging the decay of EPP amplitude. The total sum of these EPPs, reflecting the readily releasable pool of vesicles and its refilling, however, was not changed. The results suggest that adenosine inhibits a Ca2+ -independent step of transmitter exocytosis at frog motor nerve terminals. [ABSTRACT FROM AUTHOR]

Objective: To explore clinical efficacy of F-type forceps for assisted reduction in femoral shaft fracture reduction., Methods: Forty-five patients with femoral shaft fracture treated with intramedullary nail and internal fixation from January 2019 to December 2021 were retrospectively analyzed and divided into two groups according to different reduction methods. In observation group, there were 21 patients, included 15 males and 6 females, aged from 27 to 92 years old with an average of (53.38±18.81) years old;9 patients on the left side, 12 patients on the right side;7 patients were type A, 8 patients were type B and 6 patients were type C according to AO fracture classification;the time from injury to operation ranged from 7 to 13 days with an average of (4.62±3.34) days;reduction was assisted by F-shaped forceps. In control group, there were 24 patients, including 17 males and 7 females, aged from 20 to 92 years old with an average of (51.96±20.43) years old;12 patients on the left side, 12 patients on the right side;11 patients were type A, 8 patients were type B and 5 patients were type C according to AO fracture classification;the time from injury to operation ranged from 2 to 13 days with an average of (6.29±3.04) days;traditional reset mode was adopted. Operative time, intraoperative blood loss, intraoperative fluoroscopy times, intraoperative open reduction ratio, clinical healing time of fracture, postoperative complications, hospital stay, hospital cost and Lysholm score of knee joint at 6 and 12 months after surgery were compared between two groups to evaluate clinical effect., Results: All patients were followed up for 12 to 24 months with an average of (16.60±3.45) months. In observation group, operative time, intraoperative blood loss, intraoperative fluoroscopy times, open reduction cases, and clinical healing time of fractures were (58.19±7.93) min, (88.10±44.45) ml, (25.29±5.54) times, 0 case, (4.76±0.77) months, respectively;while in control group was (79.33±22.94) min, (222.92±144.45) ml, (47.46±26.25) times, 5 cases, (7.13±1.80) months, and the difference between two groups were statistically significant ( P <0.05). There were no significant difference in postoperative complications, length of stay and hospitalization cost between two groups ( P >0.05). At 6 months after surgery, Lysholm score of knee joint in observation group (88.62±4.48) was better than that in control group (79.21±8.91) ( F =21.948, P =0.000). There were no significant difference in support use, pain and squat score between two groups ( P >0.05). At 12 months after surgery, Lysholm scores of stair climbing and pain in observation group were (9.62±1.20) and (19.76±1.92), which were better than those in control group (7.83±2.04) and (21.88±2.88) ( P <0.05). There were no significant difference in scores and total scores of other items between two groups ( P >0.05)., Conclusion: Compared with traditional reduction method, F-type forceps instrument could shorten operation time, reduce intraoperative blood loss, reduce intraoperative fluoroscopy times, accelerate clinical healing of fracture, and promote earlier functional recovery of knee joint.

Epidemiological studies show that individuals with obesity are more likely to develop Alzheimer's disease (AD) than those who do not have obesity. However, the mechanisms underlying the relationship between obesity and AD are not entirely unclear. Here, we have reviewed and analyzed relevant articles published in the literature and found that obesity has correlation or potential increase in the levels of β-amyloid (Aβ) protein, which may explain why people with obesity are more likely to suffer from AD. Additionally, the published findings point to the roles of obesity-related metabolic disorders, such as diabetes, inflammation, oxidative stress, and imbalance in gut microbiota in Aβ accumulation caused by obesity. Therefore, in-depth experimental and clinical studies on these mechanisms in the future may help shed light on appropriate prevention and treatment strategies for AD, such as dietary changes and regular exercise to reverse or prevent obesity and related metabolic disorders., (© 2024 The Author(s). Published by IMR Press.)

Objective: To explore the causes of platelet aggregation in version 6.4 Trima Accel automated blood collection system and the effect of 2 intervention measures., Methods: The data on platelet aggregation ( n =61) and non-aggregation ( n =323) of 61 donors in 2020 were collected and the causes of aggregation were analyzed. Then the 72 donors with platelet aggregation in 2021 were randomized into intervention group A (increasing the anticoagulant-to-blood ratio) and intervention group B (wrapping the donor's arm with an electric blanket to keep warm and improve the blood flow speed). The collection time, average blood flow speed, number of machine alarms, anticoagulant usage, deaggregation and citrate reaction of the two groups were compared., Results: Platelet aggregation was negatively correlated with the average blood flow speed ( r =-0.394) and positively correlated with the collection time ( r =0.458). The equations for predicting aggregation and non-aggregation were constructed based on Bayesian and Fisher discriminant analysis, and the predicted accuracy was 77.1%. The comparison of the effects of two intervention measures showed that the average blood flow speed in group B was higher than that in group A; the collection time, number of machine alarms, anticoagulant usage and proportion of citrate reaction in blood donors in group B were all lower than those in Group A, all these differences were significant ( P < 0.05). In the entire cohort in 2021, 90.28% of the products were immediately deaggregated after collection, and 9.72% of the products were deaggregated within 4 hours. There was no statistically significant difference in deaggregation between the two intervention groups ( P >0.05)., Conclusion: During apheresis platelet collection, the predictive equations for aggregation and non-aggregation can be used to predict the occurrence probability of aggregation, and the intervention can be made in advance. Both intervention measures are effective in reducing platelet aggregation, however, measure B has the advantages of improving the speed of blood collection, shortening the collection time, reducing the alarm frequency and the anticoagulant usage, and reducing the incidence of citrate reaction in blood donors.

Objective: To investigate the effects of mild SARS-CoV-2 infection on hematological parameters of adult blood donors and the suitability of apheresis platelet donation, the changes of the hematological parameters in blood donors with mild infection of the SARS-CoV-2 Omicron variant strain were evaluated., Methods: Seventy-two blood donors with mild COVID-19 symptoms who donated consecutive apheresis platelets for 3 times from December 2022 to January 2023, 42 cases among which were included in the infection-positive group, and 30 cases in the suspected infection group. Forty-two donors un-vaccinated against SARS-CoV-2, un-infected, and donated three consecutive apheresis platelets from October to November 2022 were included in the control group. The changes of blood routine testing in the positive group and the suspected infection group were retrospectively compared before (Time1) and after (Time2 and Time3) the onset of symptoms, three consecutive times (Time1, Time2, Time3) in the control group by repeated measures analysis of variance. The Bayesian discriminant method was used to establish a discriminant equation to determine whether the recent infection of SARS-CoV-2 occurred or not., Results: Simple effect of the number times of tests in the positive and suspected infection groups was significant（ F infection-positive group =6.98, P < 0.001, partial η 2 =0.79, F suspected infection group =4.31, P < 0.001, partial η 2 =0.70）. The positive group and the suspected infection group had lower RBC, HCT, and HGB, and higher PLT and PCT at Time2 compared to Time1 and Time3( P < 0.05). The positive group and the suspected infection group showes RDW-CV and RDW-SD at Time3 higher than Time1 and Time2 ( P < 0.001). The simple effect of the number times of tests in the control group was not significant ( F =0.96, P =0.55, partial η 2 =0.34). The difference of the whole blood count parameters in the control group for three times was not statistically significant ( P >0.05). We established a discriminant equation to determine whether the recent infection of SARS-CoV-2 occurred or not. The equation had an eigenvalue of 0.22, a canonical correlation of 0.43 (χ 2 =27.81, P < 0.001), and an analysis accuracy of 72.9%., Conclusion: The hematological indicators of RBC, HCT, HGB, PLT, PCT, RDW-CV and RDW-SD in blood donors who had infected with mild COVID-19 showed dynamic changes. The discriminant equation for whether they are infected recently with COVID-19 has a high accuracy rate.

Objective: To investigate the clinical effect of subchondral blocking technique combined with plate and screw biplane fixation in the treatment of complex acetabular posterior wall fractures., Methods: From July 2015 to December 2019, a total of 47 cases of acetabular posterior wall fractures were treated. According to the different internal fixation techniques, they were divided into the external blocking fixation group supported by lateral plate and screw(control group of 23 cases) and the subchondral blocking technique combined with lateral plate and screw support biplane fixation group(study group of 24 cases). In the control group, there were 15 males and 8 females, aged 18 to 68 years old with an average of (40.9±7.2) years;preoperative preparation was 4 to 13 days with an average of (7.9±1.5) days. In the study group, there were 14 males and 10 females, aged 20 to 71 years old with an average of (41.7±7.9) years;preoperative preparation was 4 to 12 days with an average of (7.5±1.9) days. Kocher-Langenbeck approach was used in both groups and all patients were followed up for at least 1 year. The operation time, intraoperative blood loss, hospitalization time, quality of fracture reduction after operation, modified Merle D'Aubigne Postel score of hip joint one year after operation and postoperative complication rate of two groups were statistically analyzed and compared., Results: The patients in both groups were followed up for at least 1 year. One year after operation, the Merled'Aubigne Postel score(16.042±1.517) of hip function improvement in the study group was significantly higher than that in the control group (14.696±1.222)( P <0.05). There was no significant difference in operation time and intraoperative bleeding between the two groups( P >0.05). One year after operation, there was a significant difference between two groups in the evaluation results of Matta fracture reduction quality( P <0.05). There was no significant difference in postoperative complications between two groups( P >0.05)., Conclusion: The treatment of complex acetabular posterior wall fracture with subchondral blocking technique combined with plate and screw biplane fixation technique has lower postoperative complication rate, better functional recovery of hip joint and satisfactory clinical effect.

Objective: To assess the clinical efficacy of minimally invasive technology with trajectory screw fixation for fragility fractures of pelvic(FFP)., Methods: A retrospective case control study was performed to analyze the clinical data of 35 patients with FFP who were treated and followed up between January 2016 and December 2019. There were 12 males and 23 females, aged from 65 to 99 years with an average of(75.4±7.8) years old. There were 13 cases of type Ⅱb, 7 cases of type Ⅱc, 8 cases of type Ⅲa, 2 cases of type Ⅲb, 2 cases of type Ⅲc, 1 case of type Ⅳb, and 2 cases of type Ⅳc according to Rommens FFP comprehensive classification. All patients received the treatment of minimally invasive technology with trajectory screws fixation. According to the different methods of anterior pelvic ring fixation, FFP patients were divided into two groups:12 cases were fixed with the pedicle screw rod system in the anterior pelvic subcutaneous internal fixator (INFIX) group;23 cases were fixed with hollow screws of the pubic symphysis, superior ramus of pubis or acetabular anterior column in the screw group. The operation time, intraoperative blood loss, intraoperative fluoroscopy times, length of hospital stay, cost of internal fixation, pre- and post-operative visual analogue scale(VAS) were compared between the two groups. The fracture reduction quality was evaluated according to the Matta criteria, and the clinical function was evaluated by the Majeed functional scoring system respectively., Results: All patients were followed up for 12 to 39(16.5±5.4) months after surgery. There was no statistically significant difference in the operation time, intraoperative blood loss, intraoperative fluoroscopy time, and length of hospital stay between the two groups( P >0.05). As for the cost of internal fixation, the cost of internal fixation in the screw group [2 914 (2 914, 4 371) yuan] was significantly lower than that of the INFIX group [6 205 (6 205, 6 205) yuan] ( P <0.05). No significant difference was observed in the incidence of postoperative complications between the two groups ( P >0.05). There was no significant difference in VAS assessment at admission, 1 week, and 3 months after surgery between the two groups( P >0.05). However, the VAS assessment at 1 week and 3 months after surgery of the two groups were significantly better than those at admission( P <0.05). There was no significant difference in the quality of fracture reduction after the operation and the efficacy evaluation at the last follow-up between the two groups( P >0.05)., Conclusion: For the treatment of fragility fractures, minimally invasive technology with trajectory screw fixation can achieve good clinical efficacy. It has the advantages of being relatively minimally invasive, less bleeding, relieving the pain. It deserves clinical application.

Objective: To evaluate the efficacy of iliolumbar fixation in the treatment of U-shaped sacral fractures., Methods: A retrospective study was conducted on the 14 complex U-shaped sacral fractures which had been treated from January 2014 to December 2019, involved 10 males and 4 females, aged 24 to 48 (35.4±6.5) years. Fracture healing time, nerve function, clinical function and complications were observed in the patients., Results: All patients were followed up for 9 to 16(26.0±5.9) months. The complete weight-bearing time for bone healing was(12.4±2.0) weeks. One case of surgical incision infection occurred after operation, and one case of sacrum nailspenetrated to the outer plate of sacrum. No complications such as pressure ulcers, loosening or rupture of internal fixation occurred. According to Gibbons scoring, the neurological function recovered from preoperative 2.9±0.9 to postoperative 2.1±1.1, there were statistically significant differences between preoperative and postoperative ( t =6.9, P =0.00). There was significant difference between preoperative malformation angle (41.4±11.2)° and postoperative value (28.3±7.5)° ( t =4.70, P =0.00). According to Majeed scoring to evaluate the clinical function, postoperative pain, standing, sitting, sexual life, work ability, total score respectively were 23.21±3.17, 25.57± 3.94, 7.71±1.54, 2.64±0.92, 16.14±2.41, 75.30±8.10, 2 cases got excellent results, 10 good, 2 fair., Conclusion: Sacral lumbar fixation is an effective method for the treatment of U-shaped sacrum fractures. It has the advantages of strong internal fixation and satisfactory functional recovery.

Objective: To compare the clinical efficacy of three minimally invasive methods of anterior column screw, plate and screw rod system in the treatment of anterior pelvic ring fracture., Methods: From December 2015 to September 2018, 77 patients with pelvic anterior ring fracture were treated and followed up, including 45 males and 32 females, aged 19 to 73 years. According to AO / OTA classification, there were 26 cases of type B1, 20 cases of type B2, 17 cases of type B3 and 14 cases of type C. According to the different internal fixation methods, they were divided into three groups:anterior column screw group(35 cases), plate group(20 cases), and screw rod system group(22 cases). The operation time, intraoperative fluoroscopy times, blood loss, fracture reduction quality, complications and curative effect of the three groups were compared., Results: All 77 patients were followed up for 12 to 33 (16.5±5.7) months. The operation time, intraoperative blood loss and incision length of anterior column screw group were significantly shorter than those of plate group and screw rod system group, and intraoperative fluoroscopy times of plate group were significantly less than those of anterior column screw group and screw rod system group ( P <0.05). There was no significant difference in the quality of fracture reduction and curative effect among the three groups( P >0.05). The incidence of complications was significant different among three group( P <0.05)., Conclusion: Minimally invasive internal fixation with anterior column screw, plate and screw rod system can obtain good clinical effect, but anterior column screw fixation has less trauma and lower incidence of surgicalcomplications.