Biphasic Scaffold Loaded With Autologous Cartilage Yields Better Clinical Outcome and Magnetic Resonance Imaging Filling Compared With Marrow Stimulation for Focal Osteochondral Lesions in the Knee.

PURPOSE: To evaluate the effectiveness of marrow stimulation (MS) versus biphasic scaffold loaded with autologous cartilage (scaffold) in treating focal osteochondral lesions of the knee. METHODS: In total, 54 patients with symptomatic focal chondral or osteochondral lesion in the knee were randomized to either the scaffold group or the MS group. International Knee Documentation Committee subjective score, the Knee Injury Osteoarthritis Outcome Score, and magnetic resonance imaging (MRI) were assessed preoperatively and at 1 and 2 years after operation to compare treatment outcomes. Biopsy and second-look arthroscopy were performed at 1 year postoperatively for consenting patients. RESULTS: There were 27 patients (mean age 31.33 ± 10.95 years) in the scaffold group, and 27 patients (31.74 ± 11.44) in the MS group. The scaffold group and the MS group both included 23 patients with lesions ≤12.5 × 12.5 mm2 mm in size. In addition, each group had 4 patients with lesions between than 12.5 × 12.5 mm2 and ≤12.5 × 25 mm2. Both interventions achieved significant improvement in clinical outcome scores at 2 years. The scaffold group had greater International Knee Documentation Committee score than the MS group at 2 years (93.85 ± 9.55 vs 92.11 ± 9.84) and in the Symptoms/Stiffness and Sport/Recreation subscales of Knee Injury Osteoarthritis Outcome Score at 2 years (96.57 ± 5.97 vs 93.57 ± 6.52, P < .05) and (90.2 ± 17.76 vs 82.8 ± 16.08, P < .05). CONCLUSIONS: The use of biphasic scaffold loaded with autologous cartilage in treating focal osteochondral lesions demonstrates superior clinical outcomes and better cartilage refill on magnetic resonance imaging at the 2-year follow-up compared to marrow stimulation. LEVEL OF EVIDENCE: Level I, Randomized controlled trial.

Postoperative Rehabilitation after Anterior Cruciate Ligament Reconstruction through Telerehabilitation with Artificial Intelligence Brace during COVID-19 Pandemic.

BACKGROUND: Due to the rapid spread of the coronavirus disease-19 (COVID-19), most of the patients expressed a reluctance to undergo postoperative rehabilitation at a rehabilitation clinic. Therefore, in this scenario it was necessary to reshape the crucial role of postoperative rehabilitation of these patients. We conducted a telerehabilitation program based on an artificial intelligence brace (AI brace) which can monitor the progress of rehabilitation through an app and an internet server. Our hypothesis was that home-based telerehabilitation might provide clinical outcomes comparable to face-to-face, hospital-based rehabilitation programs in terms of effectiveness. METHODS: A retrospective cohort study enrolled patients who received anterior cruciate ligament reconstruction (ACLR) between January and September 2020. Patients were divided into two groups: the tele-AI group received telerehabilitation with an AI brace while the FTF group had face-to-face, hospital-based rehabilitation. Clinical knee functional scores and Tegner Activity Scale (TAS) were assessed and analyzed until 12 months after the operation. RESULTS: The tele-AI group had higher IKDC scores at 3 months (p = 0.0443) and 6 months (p = 0.0052) after surgery and higher KOOS scores at 1 month (p = 0.0365) and 6 months (p = 0.0375) after surgery. However, no significant difference between the two groups was detected at the end of the follow-up. The tele-AI group had higher TAS than FTF group after 1 year. CONCLUSIONS: Telerehabilitation after ACLR seems to provide a superior short-term outcome compared to hospital-based rehabilitation during the COVID-19 pandemic.

Divergent responses of cropland soil organic carbon to warming across the Sichuan Basin of China.

Cropland soils are considered to have the potential to sequester carbon (C). Warming can increase soil organic C (SOC) by enhancing primary production, but it can also cause carbon release from soils. However, the role of warming in governing cropland SOC dynamics over broad geographic scales remains poorly understood. Using over 4000 soil samples collected in the 1980s and 2010s across the Sichuan Basin of China, this study assessed the warming-induced cropland SOC change and the correlations with precipitation, cropland type and soil type. Results showed mean SOC content increased from 11.10 to 13.85 g C kg-1. Larger SOC increments were observed under drier conditions (precipitation < 1050 mm, dryland and paddy-dryland rotation cropland), which were 1.67-2.23 times higher than under wetter conditions (precipitation > 1050 mm and paddy fields). Despite the significant associations of SOC increment with crop productivity, precipitation, fertilization, cropland type and soil type, warming also acted as one of major contributors to cropland SOC change. The SOC increment changed parabolically with the rise in temperature increase rate under relatively drier conditions, while temperature increase had no impact on cropland SOC increment under wetter conditions. Meanwhile, the patterns of the parabolical relationship varied with soil types in drylands, where the threshold of temperature increase rate, the point at which the SOC increment switched from increasing to decreasing with warming, was lower for clayey soils (Ali-Perudic Argosols) than for sandy soils (Purpli-Udic Cambosols). These results illustrate divergent responses of cropland SOC to warming under different environments, which were contingent on water conditions and soil types. Our findings emphasize the importance of formulating appropriate field water management for sustainable C sequestration and the necessity of incorporating environment-specific mechanisms in Earth system models for better understanding of the soil C-climate feedback in complex environments.

Validation and modification of the Coronal Plane Alignment of the Knee classification in the Asian population.

AIMS: The Coronal Plane Alignment of the Knee (CPAK) classification is a simple and comprehensive system for predicting pre-arthritic knee alignment. However, when the CPAK classification is applied in the Asian population, which is characterized by more varus and wider distribution in lower limb alignment, modifications in the boundaries of arithmetic hip-knee-ankle angle (aHKA) and joint line obliquity (JLO) should be considered. The purposes of this study were as follows: first, to propose a modified CPAK classification based on the actual joint line obliquity (aJLO) and wider range of aHKA in the Asian population; second, to test this classification in a cohort of Asians with healthy knees; third, to propose individualized alignment targets for different CPAK types in kinematically aligned (KA) total knee arthroplasty (TKA). METHODS: The CPAK classification was modified by changing the neutral boundaries of aHKA to 0° ± 3° and using aJLO as a new variable. Radiological analysis of 214 healthy knees in 214 Asian individuals was used to assess the distribution and mean value of alignment angles of each phenotype among different classifications based on the coronal plane. Individualized alignment targets were set according to the mean lateral distal femoral angle (LDFA) and medial proximal tibial angle (MPTA) of different knee types. RESULTS: A very high concentration, 191 from 214 individuals (89.3%), were found in knee types with apex distal JLO when the CPAK classification was applied in the Asian population. By using aJLO as a new variable, the high distribution percentage in knee types with apex distal JLO decreased to 125 from 214 individuals (58.4%). The most common types in order were Type II (n = 70; 32.7%), Type V (n = 55; 25.7%), and Type I (n = 46; 21.5%) in the modified CPAK classification. CONCLUSION: The modified CPAK classification corrected the uneven distribution when applying the CPAK classification in the Asian population. Setting individualized TKA alignment targets according to CPAK type may be a practical method to recreate optimal LDFA and MPTA in KA-TKA. Cite this article: Bone Jt Open 2022;3(3):211-217.

Factors affecting cadmium accumulation in the soil profiles in an urban agricultural area.

Soil Cd pollution is a serious environmental issue associated with human activities. However, the factors determining exogenous Cd dynamics in the soil profile in a complex environment are not well understood. Based on regional observations from 169 soil profiles across the Chengdu Plain, this study explored the key factors controlling Cd accumulation in the soil profile under actual field conditions. Results showed that total soil Cd contents decreased from 0.377 to 0.196 mg kg-1 with increasing soil depth. The effects of phosphate fertilizer rates, road density and precipitation on the difference in total soil Cd content were only observed in topsoil, while agricultural land-use type and topography had no impact. In contrast, significant differences in the total soil Cd content among different parent material types were found in the 0-20, 40-60 and 60-100 cm soil depths. One sample t-tests showed that significant Cd accumulation occurred in the whole soil profile in soils formed from Q4 (Quaternary Holocene) grey alluvium, while soils formed from Q3 (Quaternary Pleistocene) old alluvium and Q4 grey-brown alluvium showed significant Cd accumulation only in the 0-40 cm soil layers. In the topsoil, acid soluble Cd accounted for the largest proportion of the total Cd in soils formed from Q4 grey alluvium, reducible Cd was the main fraction in soils formed from Q4 grey-brown alluvium, while reducible Cd and residual Cd contributed the largest proportion of the total soil Cd in soils formed from Q3 old alluvium. The above results indicated that parent material was the decisive factor determining the magnitudes and depths of exogenous Cd accumulation in the soil profile due to its impacts on the Cd fraction distributions. These findings suggested that the parent material-induced Cd fraction distributions and accumulation should be considered for effectively exploring targeted remediation strategies for Cd pollution.

The influence of processing sequence and frozen storage on the seasoned alaska pollack (Theragra chalcogramma) roe product quality.

The quality of seasoned products of Alaska pollack (Theragra chalcogramma) roe declined dramatically during frozen storage. This research investigated the effects of processing sequence and frozen storage period on seasoned Alaska pollack roe product quality. In addition, the relationship between mechanical properties and protein composition of ovary membrane and eggshell was discussed. The seasoned roe product made by the Seasoning-Frozen storage process showed higher mechanical property values, better surface color and more stable protein composition. The results clarified that this process allowed endogenous transglutaminase to act before it had been denatured and effectively prevented protein degradation during frozen storage. The retardation of protein degradation was probably attributed to cryoprotective effects from components in seasoning solution.

Biomechanical comparisons of different diagonal screw designs in a novel embedded calcaneal slide plate.

BACKGROUND: Medial displacement calcaneal osteotomy (MDCO) is frequently used for the surgical correction of flatfoot. This study aims to investigate the biomechanical effect of the different diagonal screw design on a novel-designed embedded calcaneal plate for MDCO using finite element analysis (FEA), mechanical test and digital image correlation (DIC) measurement. METHODS: Four groups according to the varied implanted plate were set as control group (Group 1), non-diagonal screw (Group 2), one-diagonal screw (Group 3), and two-diagonal screws groups (Group 4). For FEA, A 450 N load was applied to on the anterior process of the calcaneus from top to bottom. Observational indices included the stress on the cortical and cancellous bone of the calcaneus surrounding the implant, the plate itself as well as screws, and the displacement of the overall structure. In addition, this study also used in vitro biomechanics test to investigate the stiffness of the structure after implantation, and used DIC to observe the displacement of the calcaneus structure after external force. RESULTS: Under a simulated load in FEA, there are significant overall instability and high stress concentration on the calcaneal surrounding host bone and the plate/screws system, respectively, in group 2 compared with other groups. Regard to the mechanical testing with DIC system, significant increased rotation stability, maximum force and stiffness with the addition of diagonal screws. In comparison to Group 2, the increase of 112% and 157% in maximum force as well as 104% and 176% in stiffness were found in Group 3 and 4, respectively. CONCLUSION: For reducing stress concentration and enhancing overall stability, more than one-diagonal screw design is recommended and two-diagonal screws design will be superior. This study provided biomechanical references for further calcaneal implants design to prevent clinical failure after MDCO.

Effect of introducing biologics to patients with rheumatoid arthritis on the risk of venous thromboembolism: a nationwide cohort study.

In the United States, 100,000-300,000 patients die from venous thromboembolism (VTE) each year, with more than 500,000 people related hospitalizations. While in Europe, 500,000 people die from VTE each year. Patients with rheumatoid arthritis are at increased risk of VTE. The use of biologics in patients with rheumatoid arthritis may be associated with an increased risk of VTE. We identified all patients who had been newly approved for Catastrophic Illness Card of rheumatoid arthritis extracted the claims data from the National Health Insurance research database and Registry for Catastrophic Illness Patient Database from 2003 to 2016. VTE was defined as the presence of inpatient VTE diagnostic codes (including DVT or PE) according to the discharge diagnosis protocol. An analysis of VTE variables indicated that the incidence of VTE in the biologic group (14.33/10,000 person-years) was higher than that in the conventional drug group (12.61/10,000 person-years). As assessed by the Cox proportional hazards model, the relative HR for VTE in the biologic group (HR: 1.11; 95% CI 0.79-1.55) versus that in the conventional drug group did not reach a significant difference. In conclusion, this study found no significant differences in risk were observed between the use of conventional DMARDs and biologics.

Modified Superior Capsule Reconstruction Using the Long Head of the Biceps Tendon as Reinforcement to Rotator Cuff Repair Lowers Retear Rate in Large to Massive Reparable Rotator Cuff Tears.

PURPOSE: To retrospectively assess the clinical outcomes of the patients with large to massive reparable RCTs treated by arthroscopic rotator cuff repair (ARCR) combined with modified superior capsule reconstruction (mSCR) using the long head of biceps tendon (LHBT) as reinforcement with a minimum of 2 years of follow-up. METHODS: We retrospectively evaluated 40 patients with large to massive reparable RCTs who underwent ARCR and mSCR (group I) between February 2017 and June 2018 (18 patients) or underwent ARCR and tenotomy of LHBT performed at the insertion site (group II) between January 2015 and January 2017 (22 patients). The pain visual analog score (VAS) was assessed preoperatively and 1, 3, 6, 12, 24 months postoperatively. American Shoulder and Elbow Surgeons (ASES) scores, the University of California, Los Angeles (UCLA) shoulder rating scale, and active range of motion (AROM) were assessed before surgery and 6, 12, and 24 months after surgery. The integrity of the rotator cuff and mSCR was evaluated using magnetic resonance images at 12 months postoperatively. RESULTS: After surgery, both groups had significantly improved in VAS, ASES, UCLA and AROM scores in the final follow-up. There were no significant between-group differences in the characteristics of the patients before surgery. Group I had improved pain relief at 1 month (P < .001) and at 3 months (P < .01) after surgery. For the AROM, group I (flexion, external rotation, internal rotation) demonstrated better improvement than group II 6 months after surgery (all P < .05) and better internal rotation 12 and 24 months after surgery (all P < .05). The mSCR survival rate was 94.4% (17/18). The retear rate of repaired rotator cuffs for groups I and II was 16.7% (3/18) and 40.9% (9/22), respectively, and the differences were significant (P < .046). CONCLUSIONS: ARCR combined with mSCR using LHBT as reinforcement may lead to a lower retear rate and earlier functional recovery than conventional ARCR with tenotomy of LHBT for large to massive reparable RCTs. LEVEL OF EVIDENCE: Level III, retrospective therapeutic comparative trial.

The Prevention of Periprosthetic Joint Infection in Primary Total Hip Arthroplasty Using Pre-Operative Chlorhexidine Bathing.

Periprosthetic joint infection (PJI) after total hip arthroplasty (THA) is a devastating complication. The aim of this study was to investigate whether preoperative bathing using chlorhexidine gluconate (CHG) before THA can effectively reduce the postoperative PJI rate. A total of 933 primary THA patients, with the majority being female (54.4%) were included in the study. Primary THA patients who performed preoperative chlorhexidine bathing were assigned to the CHG group (190 subjects), and those who did not have preoperative chlorhexidine bathing were in the control group (743 subjects). The effects of chlorhexidine bathing on the prevention of PJI incidence rates were investigated. Differences in age, sex, and the operated side between the two groups were not statistically significant. Postoperative PJI occurred in four subjects, indicating an infection rate of 0.43% (4/933). All four infected subjects belonged to the control group. Although the PJI cases were significantly more in the control group than in the CHG group, statistical analysis revealed no statistical significance in the risk of PJI occurrence between the two groups (p = 0.588). Preoperative skin preparation by bathing with a 2% chlorhexidine gluconate cleanser did not produce significant effects on the prevention of postoperative PJI in primary THA.

Posterior cruciate ligament reconstruction implemented by the Ligament Advanced Reinforcement System over a minimum follow-up of 10 years.

PURPOSE: This study evaluated the long-term clinical follow-up results of patients who underwent double-bundle posterior cruciate ligament (PCL) reconstruction using the Ligament Advanced Reinforcement System (LARS). METHODS: Patients were assessed using clinical scores that included the Tegner activity level scale, the Lysholm score, and the International Knee Documentation Committee (IKDC) score. KT-1000 was adopted to assess stability. Radiographs and magnetic resonance imaging (MRI) were used to evaluate osteoarthritis and LARS condition. RESULTS: This study examined 38 patients, of which follow-up procedures were completed for 33 patients, resulting in a follow-up rate of 86.8%. The average follow-up period was 11.9 ±â€¯1.2 years (range: 10.3-14.2 years). The median scores of the clinical scales were as follows: Tegner activity score, 6 (range: five to seven); Lysholm score, 90 (range: 67-100); and IKDC score, 89.7 (range: 46-100). The median of the side-to-side difference (SSD) was four millimeters (range: 0-10 mm). In radiographs, the moderate OA rate was 6.9%. MRI results revealed that 26 patients exhibited ingrowth and 11 patients exhibited partial rupture of the LARS. With SSD ≤ 3 mm set as the standard for successful knee stabilization, the optimal cutoff point of LARS midsubstance thickness in the receiver operating characteristic (ROC) curve analysis was 14.3 mm. CONCLUSIONS: Long-term follow-up of the studied patients demonstrated the durability of LARS. However, clinical outcomes showed no enhancement using LARS, so it is not recommended for routine use in PCL reconstruction. LEVEL OF EVIDENCE: IV.

Effect of time interval from diagnosis to treatment for cervical cancer on survival: A nationwide cohort study.

OBJECTIVES: Despite the ease of health care access and the waiver of copayments for cancer patients, treatment is delayed in a small proportion of Taiwanese patients diagnosed with cervical cancer. In this study, we explored the relationship between the time interval from diagnosis to treatment and survival in cervical cancer patients. MATERIAL AND METHODS: The study was a retrospective population-based observational study conducted between 2004 and 2010. In Taiwan, 12,020 patients were newly diagnosed with cervical cancer from 2004 to 2010, and 9,693 patients (80.6%) were enrolled in our final analysis. RESULTS: Most of the patients received treatment within 90 days of diagnosis (n = 9,341, 96.37%). After adjustment for other variables, patients who received treatment between 90 and 180 days and >180 days after diagnosis had a 1.33 (95% CI: 1.02-1.72, P < 0.05) and 1.36 (95% CI: 1.12-1.65, P < 0.05) times higher risk of death, respectively, than those who received treatment within 90 days. Kaplan-Meier analysis showed that the patients treated after 90 days from diagnosis had a lower overall survival rate than those treated within 90 days. In analysis stratifying the patients according to their initial tumor stage, namely stages I and II and stage III and IV, the time interval from diagnosis to treatment remained a significant prognosticator in those who received treatment >180 days after diagnosis. CONCLUSION: A longer interval between diagnosis and treatment is associated with poorer prognosis among cervical cancer patients.

Ouabain induces apoptotic cell death in human prostate DU 145 cancer cells through DNA damage and TRAIL pathways.

Ouabain, a cardiotonic steroid and specific Na+ /K+ -ATPase inhibitor, has a potential to induce cancer cell apoptosis but the mechanisms of apoptosis induced by ouabain are not fully understand. The aim of this study was to investigate the cytotoxic effects of ouabain on human prostate cancer DU 145 cells in vitro. Cell morphological changes were examined by phase contrast microscopy. Cell viability, cell cycle distribution, cell apoptosis, DNA damage, the production of ROS and Ca2+ , and mitochondrial membrane potential (ΔΨm ) were measured by flow cytometry assay. Results indicated that ouabain induced cell morphological changes, decreased total cell viability, induced G0/G1 phase arrest, DNA damage, and cell apoptosis, increased ROS and Ca2+ production, but decreased the levels of ΔΨm in DU 145 cells. Ouabain also increased the activities of caspase-3, -8, and -9. Western blotting was used for measuring the alterations of apoptosis-associated protein expressions in DU 145 cells and results indicated that ouabain increased the expression of DNA damage associated proteins (pATMSer1981 , p-H2A.XSer139 , and p-p53Ser15 ) and ER-stress-associated proteins (Grp78, ATF6ß, p-PERKThr981 , PERK, eIF2A, GADD153, CaMKIIß, and caspase-4) in time-dependently. Furthermore, ouabain increased apoptosis-associated proteins (DR4, DR5, Fas, Fas Ligand, and FADD), TRAIL pathway, which related to extrinsic pathway, promoted the pro-apoptotic protein Bax, increased apoptotic-associated proteins, such as cytochrome c, AIF, Endo G, caspase-3, -8, and -9, but reduced anti-apoptotic protein Bcl-2 and Bcl-x in DU 145 cells. In conclusion, we may suggest that ouabain decreased cell viability and induced apoptotic cell death may via caspase-dependent and mitochondria-dependent pathways in human prostate cancer DU 145 cells.

Texture enhancement of salted Alaska pollock (Theragra chalcogramma) roe using microbial transglutaminase.

The aim of our study was to improve the texture quality of salted Alaska pollock (Theragra chalcogramma) roe product using microbial transglutaminase (MTGase). Thus, the effect of 0-1.0% MTGase on the physical properties of the salted roe was assessed. Endogenous TGase activity in the roe, which contributes to improving its texture, decreased at -20 °C during frozen storage. Mechanical properties of the salted roe, such as roe firmness and egg breaking strength, were improved using MTGase, the optimum concentration of which was 0.5%. Protein polymerizations using SDS-PAGE and decreasing of protein solubilities in SDS-urea solution were observed in the salted roe with MTGase. Therefore, the texture of salted Alaska pollock roe can be significantly enhanced by adding 0.5% MTGase because of catalyzing protein crosslinking. Additionally, this study most likely indicates that MTGase can be used to improve the texture of aquatic processed foods at low temperatures, especially 5 °C.

Activity-related outcome in anterior cruciate ligament reconstruction with synthetic ligament advanced reinforcement system.

BACKGROUND: Arthroscopic anterior cruciate ligament (ACL) reconstruction with ligament advanced reinforcement system (LARS) had revealed good results with low complication and failure rate in series of studies. The specific candidates for ACL reconstruction with LARS are still unknown anyway. The purpose of this study is to evaluate the activity-related outcome in ACL reconstruction using LARS ligament. METHODS: A total of 43 unilateral arthroscopic ACL reconstructions with LARS were collected and divided into two groups: group A (preinjury Tegner score ≥ 6, n = 20) and group B (preinjury Tegner score < 6, n = 23). We had analyzed the stability of knee and functional outcome with a minimum of 2-years follow up. RESULTS: All patients were aware of improvement over the knee stability immediately after ACL reconstruction with LARS. The functional outcome of knee was improved in both groups by analysis with the Lysholm score and modified International Knee Documentation Committee (IKDC) score. The postoperative grading of the knee examination form of modified IKDC grade showed no statistical difference in both groups. CONCLUSION: Arthroscopic ACL reconstruction with LARS was encouraged as an alternative option even in high sports demand patients.

Targeting HIV-1 Protease Autoprocessing for High-throughput Drug Discovery and Drug Resistance Assessment.

HIV-1 protease autoprocessing liberates the free mature protease from its Gag-Pol polyprotein precursor through a series of highly regulated autoproteolysis reactions. Herein, we report the development and validation (Z' ≥ 0.50) of a cell-based functional assay for high-throughput screening (HTS) of autoprocessing inhibitors using fusion precursors in combination with AlphaLISA (amplified luminescent proximity homogeneous assay ELISA). Through pilot screening of a collection of 130 known protease inhibitors, the AlphaLISA assay confirmed all 11 HIV protease inhibitors in the library capable of suppressing precursor autoprocessing at low micromolar concentrations. Meanwhile, other protease inhibitors had no impact on precursor autoprocessing. We next conducted HTS of ~23,000 compounds but found no positive hits. Such high selectivity is advantageous for large-scale HTS campaigns and as anticipated based on assay design because a positive hit needs simultaneously to be nontoxic, cell permeable, and inhibiting precursor autoprocessing. Furthermore, AlphaLISA quantification of fusion precursors carrying mutations known to cause resistance to HIV protease inhibitors faithfully recapitulated the reported resistance, suggesting that precursor autoprocessing is a critical step contributing to drug resistance. Taken together, this reported AlphaLISA platform will provide a useful tool for drug discovery targeting HIV-1 protease autoprocessing and for quantification of PI resistance.

Approximation formulas related to Somos' quadratic recurrence constant.

We present two classes of asymptotic expansions related to Somos' quadratic recurrence constant and provide the recursive relations for determining the coefficients of each class of the asymptotic expansions by using Bell polynomials and other techniques. We also present continued fraction approximations related to Somos' quadratic recurrence constant.

Approximations to inverse tangent function.

In this paper, we present a sharp Shafer-type inequality for the inverse tangent function. Based on the Padé approximation method, we give approximations to the inverse tangent function. Based on the obtained result, we establish new bounds for arctanx.

Bufalin Enhances Immune Responses in Leukemic Mice Through Enhancing Phagocytosis of Macrophage In Vivo.

BACKGROUND/AIM: Bufalin, bufadienolide present in Chan Su, has been shown to induce cancer cell apoptosis in many human cancer cells, including human leukemia cells, but its effects on immune responses are unknown. MATERIALS AND METHODS: This study investigated whether bufalin affected immune responses of mice with WEHI-3 cell-generated leukemia in vivo. BALB/c mice were intraperitoneally injected with WEHI-3 cells to develop leukemia and then were treated with oral treatment with bufalin at different doses (0, 0.1, 0.2 and 0.4 mg/kg) for 2 weeks. At the end of treatment, all mice were weighted and blood was collected; liver and spleen tissues were collected for cell marker, phagocytosis, natural killer (NK) cell activity and T- and B-cell proliferation measurements by using flow cytometric assays. RESULTS: When compared with the leukemia control group, bufalin increased the body weight, but reduced liver and spleen weights, and reduced CD3, CD16 and Mac-3 cell markers at 0.4 mg/kg treatment and increased CD11b marker at 0.1 and 0.2 mg/kg treatment. Furthermore, bufalin at 0.4 mg/kg increased phagocytosis by macrophages isolated from peripheral blood mononuclear cells and at 0.1 mg/kg by those from the peritoneal cavity. Bufalin (0.2 and 0.4 mg/kg) increased NK cell cytotoxic activity at effector:target ratio of 50:1. Bufalin increased B-cell proliferation at 0.1 and 0.2 mg/kg treatment but only increased T-cell proliferation at 0.1 mg/kg. Bufalin increased glutamate oxaloacetate transaminase level at all dose treatments, increased glutamic pyruvic transaminase level only at 0.1 mg/kg treatment, but reduced the level of lactate dehydrogenase at all dose levels in mice with WEHI-3 cell-induced leukemia in vivo. CONCLUSION: Bufalin increased immune responses by enhancing phagocytosis in mice with leukemia mice.

Inequalities and asymptotic expansions related to the generalized Somos quadratic recurrence constant.

In this paper, we give asymptotic expansions and inequalities related to the generalized Somos quadratic recurrence constant, using its relation with the generalized Euler constant.