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Aim: To explore the risk factors for acute acquired comitant esotropia (AACE)., Methods: A retrospective cohort study was conducted by analyzing 83 patients (case group) with AACE who underwent strabismus correction surgery from January 1, 2021 to June 30, 2022. Totally 73 outpatient volunteers were recruited during the same period as the normal control group. The case group's binocular vision time, near and distance esotropia angle, and near stereo vision function were recorded, and the age, gender, refractive status, and best-corrected visual acuity (BCVA) of both groups were analyzed. Additionally, multiple logistic regression analysis was conducted using an eye usage condition questionnaire to determine the independent risk factors for AACE., Results: In the case group, 61 patients (73.49%) had myopia, with a mean equivalent spherical power (SE) of -3.35±3.31 D (range: +2.75 to -10.62 D) of the right eye and -2.87±3.35 D (range: +2.75 to -11.12 D) of the left eye. The average duration of diplopia in the case group was 29.83±35.72mo, of which 80 patients (96.39%) were primarily with distance diplopia. The near and distance esotropia angle after wearing glasses were 52.36±20.95 prism degree (PD) and 56.71±19.54 PD, respectively, and there was no statistically significant difference between the two ( t =1.38, P =0.169). The incidence of improper glasses wearing and unhealthy eye habits in the case group was significantly higher than those in the control group ( P <0.05). Close-up work without glasses [ β =2.30, odds ratio (OR)=10, 95% confidence interval (CI) 2.35-42.51, P =0.002] and near work in supine position ( β =1.80, OR=6.02, 95%CI 3.29-11.02, P <0.001) were independent risk factors for AACE., Conclusion: Patients with AACE mainly present with distance diplopia, and there is a high degree of variation in myopia. Near work without wearing glasses and in supine position are independent risk factors for AACE., (International Journal of Ophthalmology Press.)

Background: Falls in older adults are the result of a complex web of interacting causes, that further results in other physical, emotional, and psychological sequelae. A conceptual framework that represents the reciprocal dynamics of these causal factors can enable clinicians, researchers, and policymakers to clarify goals in falls intervention in older adults., Methods: A Group Model Building (GMB) exercise was conducted with researchers and clinicians from academic units and public healthcare institutes in Singapore. The aim of the exercise was to produce a shared visual representation of the causal structure for falls and engage in discussions on how current and future falls intervention programmes can address falls in the older adults, especially in the Asian context. It was conducted in four steps: 1) Outlining and prioritising desirable patient outcomes, 2) Conceptual model building, 3) Identifying key intervention elements of effective falls intervention programmes, 4) Mapping of interventions to outcomes. This causal loop diagram (CLD) was then used to generate insights into the current understanding of falls causal relationships, current efforts in falls intervention in Singapore, and used to identify gaps in falls research that could be further advanced in future intervention studies., Results: Four patient outcomes were identified by the group as key in falls intervention: 1) Falls, 2) Injurious falls, 3) Fear of falling, and 4) Restricted mobility and life space. A CLD of the reciprocal relationships between risk factors and these outcomes are represented in four sub-models: 1) Fear of falling, 2) Injuries associated with falls, 3) Caregiver overprotectiveness, 4) Post-traumatic stress disorder and psychological resilience. Through this GMB exercise, the group gained the following insights: (1) Psychological sequelae of falls is an important falls intervention outcome. (2) The effects of family overprotectiveness, psychological resilience, and PTSD in exacerbating the consequences of falls are not well understood. (3) There is a need to develop multi-component falls interventions to address the multitude of falls and falls related sequelae., Conclusion: This work illustrates the potential of GMB to promote shared understanding of complex healthcare problems and to provide a roadmap for the development of more effective preventive actions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background and Objectives: Falls among older adults are a significant health problem globally. Studies of multicomponent fall prevention programs in randomized controlled trials demonstrate effectiveness in reducing falls; however, the translation of research into the community remains challenging. Although there is an increasing interest to understand the factors contributing to implementation barriers, the dynamic relationships between factors are less well examined. Furthermore, evidence on implementation barriers from Asia is lacking as most of these studies originate from the West. As such, this study aims to engage stakeholders in uncovering the factors that facilitate or inhibit implementing community-based fall prevention programs in Singapore, with a focus on the interrelationship between those factors., Research Design and Methods: Health care professionals familiar with fall prevention programs were invited to discuss the enablers and challenges to the implementation. This effort was facilitated using a systems modeling methodology of Group Model Building (GMB) to share ideas and create a common conceptual model of the challenges. The GMB employs various engagement techniques to draw on the experiences and perceptions of all stakeholders involved., Results: This process led to the development of a Causal Loop Diagram (CLD), a qualitative conceptual model of the dynamic relationships between the barriers and facilitators of implementing fall prevention programs. Results from the CLD show that implementation is influenced by two main drivers: health care provider factors that influenced referrals, and patient factors that influenced referral acceptance and long-term adherence. Key leverage points for potential interventions were identified as well., Discussion and Implications: The overall recommendation emphasized closer coordination and collaboration across providers to ensure sustainable and effective community-based fall prevention programs. This has to be supported by a national effort, involving a multidisciplinary stakeholder advisory group. These findings generated would be promising to guide future approaches to fall prevention., Competing Interests: The authors have no conflict of interest to declare. Preliminary findings were presented at the 18th Biennial European Conference of the Society for Medical Decision Making (May 21–23, 2023)., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Introduction: Due to an aging population, the rising prevalence and incidence of hip fractures and the associated health and economic burden present a challenge to healthcare systems worldwide. Studies have shown that a complex interplay of physiological, psychological, and social factors often affects the recovery trajectories of older adults with hip fractures, often complicating the recovery process., Methods: This research aims to actively engage stakeholders (including doctors, physiotherapists, hip fracture patients, and caregivers) using the systems modeling methodology of Group Model Building (GMB) to elicit the factors that promote or inhibit hip fracture recovery, incorporating a feedback perspective to inform system-wide interventions. Hip fracture stakeholder engagement was facilitated through the Group Model Building approach in a two-half-day workshop of 25 stakeholders. This approach combined different techniques to develop a comprehensive qualitative whole-system view model of the factors that promote or inhibit hip fracture recovery., Results: A conceptual, qualitative model of the dynamics of hip fracture recovery was developed that draws on stakeholders' personal experiences through a moderated interaction. Stakeholders identified four domains (i.e., expectation formation, rehabilitation, affordability/availability, and resilience building) that play a significant role in the hip fracture recovery journey.., Discussion: The insight that recovery of loss of function due to hip fracture is attributed to (a) the recognition of a gap between pre-fracture physical function and current physical function; and (b) the marshaling of psychological resilience to respond promptly to a physical functional loss via uptake of rehabilitation services is supported by findings and has several policy implications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Ansah, Chia, Koh, Lai, Koh, Goh, Yeo, Howe, Seow, Mamun, Balasubramanian, Varman, Yeo, Elamin, Chan and Matchar.)

For several decades, health systems in developed countries have faced rapidly rising healthcare costs without concomitant improvements in health outcomes. Fee for service (FFS) reimbursement mechanisms (RMs), where health systems are paid based on volume, contribute to this trend. In Singapore, the public health service is trying to curb rising healthcare costs by transitioning from a volume-based RM to a capitated payment for a population within a geographical catchment area. To provide insight into the implications of this transition, we developed a causal loop diagram (CLD) to represent a causal hypothesis of the complex relationship between RM and health system performance. The CLD was developed with input from government policymakers, healthcare institution administrators, and healthcare providers. This work highlights that the causal relationships between government, provider organizations, and physicians involve numerous feedback loops that drive the mix of health services. The CLD clarifies that a FFS RM incentivizes high margin services irrespective of their health benefits. While capitation has the potential to mitigate this reinforcing phenomenon, it is not sufficient to promote service value. This suggests the need to establish robust mechanisms to govern common pool resources while minimizing adverse secondary effects.

Hypertension is prevalent among older adults (60 years and above), but control of blood pressure (BP) remains suboptimal. While there is increasing interest in using digital technology for managing hypertension, information about the extent and potential correlates of such use among older adults remains scant. We assessed the prevalence and correlates of the use of digital technology for managing hypertension among older adults with hypertension. We also investigated if the use of digital technology was associated with BP or hypertension control. The use of digital technology (internet or digital apps) for information about or managing BP or hypertension was assessed among 1729 older adults diagnosed with hypertension participating in a national survey in Singapore. Regression analysis was used to assess the correlates (based on the Unified Theory of Use and Acceptance of Technology), and whether such use was associated with hypertension control or BP values. Digital technology for managing hypertension was used by 7.1% of older adults with hypertension. Those of higher age and with limitations in one or more activities or instrumental activities of daily living were less likely, while those with secondary education and above, and with stronger social network were more likely to use digital technology. There was no association between the use of digital technology and hypertension control. While users of digital technology had lower systolic (by 2.1 mmHg, adjusted p value = 0.12) and diastolic (by 1.6 mmHg, adjusted p value = 0.13) BP than non-users, the differences were not statistically significant. Given its low prevalence, there is potential for increased use of digital technology for managing hypertension among older adults with hypertension in Singapore. Initiatives to increase digital health use should target specific older adult subgroups., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Oncogenic mutations in the RAS family of small GTPases are commonly found in human cancers and they promote tumorigenesis by altering gene expression networks. We previously demonstrated that Casein Kinase 1α (CK1α), a member of the CK1 family of serine/threonine kinases, is post-transcriptionally upregulated by oncogenic RAS signaling. Here, we report that the CK1α mRNA contains an exceptionally long 5'-untranslated region (UTR) harbouring several translational control elements, implicating its involvement in translational regulation. We demonstrate that the CK1α 5'-UTR functions as an IRES element in HCT-116 colon cancer cells to promote cap-independent translation. Using tobramycin-affinity RNA-pulldown assays coupled with identification via mass spectrometry, we identified several CK1α 5'-UTR-binding proteins, including SFPQ. We show that RNA interference targeting SFPQ reduced CK1α protein abundance and partially blocked RAS-mutant colon cancer cell growth. Importantly, transcript and protein levels of SFPQ and other CK1α 5'-UTR-associated RNA-binding proteins (RBPs) are found to be elevated in early stages of RAS-mutant cancers, including colorectal and lung adenocarcinoma. Taken together, our study uncovers a previously unappreciated role of RBPs in promoting RAS-mutant cancer cell growth and their potential to serve as promising biomarkers as well as tractable therapeutic targets in cancers driven by oncogenic RAS., (© The Author(s) 2022. Published by Oxford University Press on behalf of NAR Cancer.)

Chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for relapsed and refractory acute lymphoblastic leukemia (R/R ALL). However, autologous CAR-T cells derived from patients with B-ALL often show poor amplification ability, exhaustion, and anergy. To overcome these limitations, allogeneic CAR-T cells may be used as effective substitutes; however, which source would be the best substitute is unclear. In this study, we compared the immunophenotype and antitumor efficacy of anti-CD19 CAR-T cells derived from healthy donor cord blood (CB), healthy donor peripheral blood (PB), and PB of B-ALL patients [PB (patient)] in vitro and NOD-Prkdcem26cd52Il2rgem26Cd22/Nju (NCG)-immunodeficient mice, respectively. The results revealed that CAR-T cells derived from healthy donor CB and PB showed a higher proportion of naive T cells and longer tumor suppression in tumor-bearing mice than those of PB (patient). PB (patient) CAR-T cells had a higher proportion of regulatory T cells (Treg cells) and released high levels of interluekin-10 (IL-10), which also suggest a poor prognosis. Thus, CAR-T cells derived from healthy donors have better antitumor efficacy than CAR-T cells derived from PB (patient), and CB may be a good source of allogeneic CAR-T cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Hong, Qiu, Li, Liu, Zhu, Lai, Chen, Yang, Xu and Fang.)

Ammonium removal in wastewater treatment plants demands large quantities energy input, such as aeration for wastewater and the addition of organics for nitrate reduction. Anaerobic ammonium oxidation coupled to Fe(III) reduction, called Feammox process play a crucial role in natural nitrogen cycle, which has been rarely investigated in the field of wastewater treatment. Besides, Iron-reducing bacteria (FeRB) as function bacteria of Feammox could transfer electrons to iron oxide by oxidizing organics. The possibility of anaerobic ammonium removal coupled with organics should be investigated to assess the potential of Feammox process for conventional wastewater treatment. In this study, five Fe(III) compounds, Fe 2 O 3 , Fe 3 O 4 , Fe(OH) 3 , Citrate-Fe and pyrite were supplemented to investigate the effect of iron oxides on ammonium removal in serum bottles with working volume of 100 mL. It was found that ammonium removal efficiency of the Fe 2 O 3 group was the highest. To simulate wastewater treatment process in sewage treatment plant, three Up-flow anaerobic sludge blanket reactors with volume of 250 mL adding Fe 2 O 3 were applied with influent of ammonium and carbon sources. It was found that the organics significantly inhibited the ammonium removal by Feammox process. This was attributed to that carbon sources and ammonium could be used as electron donors for Fe(III) reduction. In addition, this nitrogen removal was also likely related with the iron cycle, i.e., Fe(III) reduction with ammonium oxidation and Fe(II) oxidation with nitrate/nitrite reduction. This study provides a promising alternative technology for anaerobic ammonium removal in wastewater treatment. Optimizing nitrogen removal and carbon sources applied in conventional wastewater plants are required in future., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Tuberculosis (TB) is a leading cause of morbidity and mortality in underdeveloped and developing countries. Disseminated TB may induce uncommon and potentially fatal secondary hemophagocytic lymphohistiocytosis (HLH). Timely treatment with anti-tuberculosis therapy (ATT) and downmodulation of the immune response is critical. However, corticosteroid treatment for TB-associated HLH remains controversial. Herein, we report a successful case of disseminated TB-associated HLH in a pregnant woman with Evans syndrome accompanied by a literature review., Case Presentation: A 26-year-old pregnant woman with Evans syndrome was transferred to the Third Affiliated Hospital of Sun Yat-Sen University because of severe pneumonia. She presented with cough, fever, and aggravated dyspnea. Nested polymerase chain reaction for Mycobacterium tuberculosis ( M. tuberculosis ) complex in sputum was positive. Sputum smear sample for acid-fast bacilli was also positive. Metagenome next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid identified 926 DNA sequence reads and 195 RNA sequence reads corresponding to M. tuberculosis complex, respectively. mNGS of blood identified 48 DNA sequence reads corresponding to M. tuberculosis . There was no sequence read corresponding to other potential pathogens. She was initially administered standard ATT together with a low dose of methylprednisolone (40 mg/day). However, her condition deteriorated rapidly with high fever, acute respiratory distress syndrome, pancytopenia, and hyperferritinemia. Bone marrow smears showed hemophagocytosis. And caseating tuberculous granulomas were found in the placenta. A diagnosis of disseminated TB-associated HLH was made. Along with the continuation of four drug ATT regimen, therapy with a higher dose of methylprednisolone (160 mg/day) combined with immunoglobulin and plasma exchange was managed. The patient's condition improved, and she was discharged on day 19. Her condition was good at follow-up with the continuation of the ATT., Conclusions: Clinicians encountering patients with suspected TB accompanied by unexplainable inflammation not responding to ATT should consider complications with HLH. Timely administration of ATT combined with corticosteroids may result in a favorable outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shi, Shi, Zhang, Chen, Lai, Luo, Ba, Wang, Chen and Wu.)

Glucocorticoid (GC)-induced osteoporosis (GIO) is characterized by impaired bone formation, which can be alleviated by tanshinol, an aqueous polyphenol isolated from Salvia miltiorrhiza Bunge. In this study we investigated the molecular mechanisms underlying GC-induced modulation of osteogenesis as well as the possibility of using tanshinol to interfere with GIO. Female SD rats aged 4 months were orally administered distilled water (Con), prednisone (GC, 5 mg·kg -1 ·d -1 ), GC plus tanshinol (Tan, 16 mg·kg -1 ·d -1 ) or GC plus resveratrol (Res, 5 mg·kg -1 ·d -1 ) for 14 weeks. After the rats were sacrificed, samples of bone tissues were collected. The changes in bone formation were assessed using Micro-CT, histomorphometry, and biomechanical assays. Expression of Kruppel-like factor 15 (KLF15), peroxisome proliferator-activated receptor γ 2 (PPARγ 2) and other signaling proteins in skeletal tissue was measured with Western blotting and quantitative RT-PCR. GC treatment markedly increased the expression of KLF15, PPARγ2, C/EBPα and aP2, which were related to adipogenesis, upregulated FoxO3a pathway proteins (FoxO3a and Gadd45a), and suppressed the canonical Wnt signaling (β-catenin and Axin2), which was required for osteogenesis. Thus, GC significantly decreased bone mass and bone quality. Co-treatment with Tan or Res effectively counteracted GC-impaired bone formation, suppressed GC-induced adipogenesis, and restored abnormal expression of the signaling molecules in GIO rats. We conclude that tanshinol counteracts GC-decreased bone formation by inhibiting marrow adiposity via the KLF15/PPARγ2/FoxO3a/Wnt pathway.

Long-term utilization of immunosuppression in organ transplant recipients leads to decreased immune-mediated tumor surveillance and increased risk of developing malignant tumors. However, chronic myeloid leukemia (CML) following living donor liver transplantation (LDLT) is rarely reported. The current case report presents a 42-year-old male patient who developed CML 14 months following LDLT. The patient achieved complete hematologic remission and early molecular response at 3 months imatinib treatment and major molecular response at 12 months imatinib treatment. The pathogenesis, risk factors, treatment and prognosis for CML following liver transplantation are unclear. Therefore, further analysis through accumulation of cases will be of great importance to prevent and treat this rare complication following liver transplantation.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal condition that can be primary or secondary. Secondary HLH due to Mycobacterium tuberculosis (TB) is uncommon. We report a case of tuberculosis-associated HLH in an umbilical cord blood transplant (UCBT) recipient and discuss its clinical characteristics and challenges., Methods: Hematologic investigations, bone marrow aspirates, Xpert MTB/RIF test of TB with peripheral blood were performed. Immune modulation with anti-TB therapy was initiated., Results: Subsequent treatment with anti-TB treatment resulted rapid clinical response and disease remission., Conclusion: It is important to consider TB as one of the underlying cause of HLH in high-risk patients, particularly those in immunodeficient states. Early diagnosis and treatment can improve the survival rates of patients with tuberculosis-associated HLH., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The whole-genome sequence of a new genospecies of Methylobacterium sp., named GXS13 and isolated from grapevine xylem sap, is reported and demonstrates potential for methylotrophy, cytokinin synthesis, and cell wall modification. In addition, biosynthetic gene clusters were identified for cupriachelin, carotenoid, and acyl-homoserine lactone using the antiSMASH server., (Copyright © 2016 Lai et al.)

In this study, we performed all-atom long-timescale molecular dynamics simulations of phospholipid bilayers incorporating three different proportions of negatively charged lipids in the presence of K(+), Mg(2+), and Ca(2+) ions to systemically determine how membrane properties are affected by cations and lipid compositions. Our simulations revealed that the binding affinity of Ca(2+) ions with lipids is significantly stronger than that of K(+) and Mg(2+) ions, regardless of the composition of the lipid bilayer. The binding of Ca(2+) ions to the lipids resulted in bilayers having smaller lateral areas, greater thicknesses, greater order, and slower rotation of their lipid head groups, relative to those of corresponding K(+)- and Mg(2+)-containing systems. The Ca(2+) ions bind preferentially to the phosphate groups of the lipids. The complexes formed between the cations and the lipids further assembled to form various multiple-cation-centered clusters in the presence of anionic lipids and at higher ionic strength-most notably for Ca(2+). The formation of cation-lipid complexes and clusters dehydrated and neutralized the anionic lipids, creating a more-hydrophobic environment suitable for membrane aggregation. We propose that the formation of Ca(2+)-phospholipid clusters across apposed lipid bilayers can work as a "cation glue" to adhere apposed membranes together, providing an adequate configuration for stalk formation during membrane fusion., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Increased macrophage vulnerability is associated with progression of systemic lupus erythematosus. Our previous studies have shown that cystamine, an inhibitor of transglutaminase 2 (TG2), alleviated the apoptosis of hepatocyte and brain cell in lupus-prone mice NZB/W-F1. In present study, we further investigated the effects of cystamine on apoptosis-prone macrophages (APMs) in the lupus mice. Using two-dimensional gel electrophoresis (2-DE) analysis, we found that cystamine induced a differential protein expression pattern of APM as comparing to the PBS control. The protein spots presenting differential level between cystamine and PBS treatment were then identified by peptide-mass fingerprinting (PMF). After bioinformatic analysis, these identified proteins were found involved in mitochondrial apoptotic pathway, oxidative stress, and mitogen-activated protein (MAP) kinase-mediated pathway. Further investigation revealed that cystamine significantly decreased the levels of apoptotic Bax and Apaf-1 and the activity of caspase-3, and increased the levels of anti-apoptotic Bcl-2 in APM. We also found that these apoptotic mediators were up-regulated in a correlation with the progression of lupus severity in NZB/W-F1, which were little affected in BALB/c mice. We also found that the reduced serum glutathione was restored by cystamine in NZB/W-F1. Interestingly, the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in APM and the phagocytic ability was diminished in presence of cystamine. In conclusion, our findings indicate that cystamine significantly inhibited mitochondrial pathway, induced antioxidant proteins, and diminished phosphorylation of extracellular ERK1/2, which may alleviate the apoptosis and the phagocytic ability of APM., ((c) 2010 Wiley-Liss, Inc.)

The involvement of the central nervous system (CNS) or neuropsychosis has been reported in patients with systemic lupus erythematosus (SLE) and considered a major cause of long-standing functional impairment and mortality. However, little is known in the improvement of the brain abnormality in SLE. To investigate the effect and mechanism of cystamine on brain in SLE, NZB/W F1 mice were used as the animal model. Gel zymography, caspase-3 activity assay and Western blots were performed to elucidate the effect of cystamine. Significant reduction of matrix metalloproteinases (MMP)-9/MMP-2 ratio and urokinase-type plasminogen activator (uPA) expression was detected in brain of NZB/W F1 mice treated with cystamine as compared to control group. Significant increase of heat-shock protein (HSP)-70 and HSP27 was detected in brain of NZB/W F1 mice treated with cystamine as compared to control group. Additionally, significant reduction of mitochondrial dependent apoptosis was observed in brain of NZB/W F1 mice treated with cystamine as compared to control group by increasing BCL-2 and reducing caspase-9, Bad, and Apaf-1 expression. Moreover, increased phosphorylated p65 (NF-kappaB) protein was observed in brain of NZB/W F1 mice treated with cystamine as compared to control group. These experimental results firstly demonstrated the beneficial effects of cystamine on brain in NZB/W F1 mice and suggested the therapeutic potential in patients with neuropsychiatric SLE (NP-SLE).

Increased population with hepatic diseases and apoptosis were found in patients with SLE and implicated in the pathogenesis of SLE. Since cystamine has been demonstrated to be beneficial to NZB/W F1 mice in our previous report, this study intends to investigate the effects of cystamine in liver from NZB/W F1 mice. Decreased apoptosis was detected in liver from NZB/W F1 mice given cystamine as compared to those given PBS by TUNEL and caspase-3 activity assay. Fas-dependent apoptotic proteins including Fas, cleaved caspase-8 and tBid were reduced in liver from NZB/W F1 mice given cystamine as compared to those given PBS. Additionally, the mitochondria-dependent apoptotic proteins including cytochrome c and Apaf-1 were reduced in liver from NZB/W F1 mice given cystamine as compared to those given PBS. Moreover, increased BCL-2 protein was observed in liver from both mice. Notably, increased NF-kappaB protein was detected in liver from NZB/W F1 mice given cystamine as compared to those given PBS. These experimental results suggest the effect of cystamine in reducing apoptosis in liver from NZB/W F1 mice through Fas-dependent and mitochondrial-dependent pathways. The phosphorylation of NF-kappaB (p65) could be a possible mechanism involving anti-apoptotic effects of cystamine in liver from NZB/W F1 mice.

Increased hepatic abnormality has been observed in patients with systemic lupus erythematosus (SLE) and contributes to the elevated apoptosis that results in severe disease activity. Since cystamine has been demonstrated to be beneficial for NZB/W F1 mice, this study investigates the effects of cystamine on various inflammatory and stress-related proteins in liver from NZB/W F1 mice. Nephelometric analyses and immunoblots were conducted to detect aspartate aminotransferase (AST), alanine aminotransferase (ALT), C-reactive protein (CRP), p53, p21, Gadd45, heat shock protein 70 (HSP70) and cyclooxygenase-2 (COX-2). AST and ALT were reduced in NZB/W F1 mice that were given cystamine and CRP, p53, p21, Gadd45, HSP70 and COX-2 proteins in the liver were reduced in NZB/W F1 mice that were treated with cystamine. Moreover, cystamine has no obvious effect on BALB/c mice. These findings suggest that cystamine reduces the inflammation in liver of NZB/W F1 mice and provide a clue in treatment of SLE with liver abnormality.