Publications by authors named "Kuan Lai"

15 Publications

  • Page 1 of 1

miR-20a Overexpression in Adipose-Derived Mesenchymal Stem Cells Promotes Therapeutic Efficacy in Murine Lupus Nephritis by Regulating Autophagy.

Stem Cells Int 2021 21;2021:3746335. Epub 2021 Oct 21.

Department of Dermatology, Nanfang Hospital, Southern Medical University, China.

Objective: Lupus nephritis is the most common and severe complication of systemic lupus erythematosus. The aim of our study was to investigate the efficacy of miR-20a overexpressing adipose-derived stem cell (ADSC) transplantation in murine lupus nephritis (LN) and explore potential molecular mechanisms.

Methods: Mouse ADSCs were transfected with a miR-20a lentiviral vector to obtain miR-20a overexpression ADSCs (miR-20a-ADSCs). We first observed the influence of miR-20a on ADSC viability and apoptosis . B6.MRL/lpr mice were administered ADSC/miR-20a-ADSC intravenously every week from age 30 to 33 weeks, and the lupus and normal control groups received PBS on the same schedule.

Results: miR-20a expression increased in miR-20a-ADSC-derived exosomes, and miR-20a overexpression promoted ADSC proliferation and inhibited apoptosis. Compared with ADSCs, miR-20a-ADSC treatment significantly improved serologic and histologic abnormalities, as evidenced by reduced serum creatinine, anti-dsDNA antibody, 24 h urine protein levels, nephritis scores, and C3/IgG deposits. Furthermore, miR-20a-ADSC treatment resulted in downregulated Akt, mTOR, and p62 expression and upregulated miR-20a, Beclin 1, and LC3 II/I expression compared with ADSC treatment. After treatment with miR-20a-ADSC, a significant increase in the number of autophagosomes within podocytes was observed, along with upregulated expression of podocin and nephrin, compared with the ADSC group.

Conclusions: miR-20a-ADSC transplantation prevents the development of lupus nephritis and significantly ameliorates already-established disease, and its mechanism is related to autophagy by targeting the miR-20a-regulated mTOR pathway.
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http://dx.doi.org/10.1155/2021/3746335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553505PMC
October 2021

mTOR pathway regulates the differentiation of peripheral blood Th2/Treg cell subsets in patients with pemphigus vulgaris.

Acta Biochim Biophys Sin (Shanghai) 2021 Mar;53(4):438-445

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Pemphigus vulgaris (PV) is a chronic and potentially life-threatening autoimmune blistering disease. Aberrant mTOR pathway activity is involved in many autoimmune diseases. This study investigated the correlation of mTOR pathway (PI3K/AKT/mTOR/p70S6K) activity with the loss of balance in T helper 2/regulatory T (Th2/Treg) cells in the peripheral blood of PV patients. CD4+ T cells were isolated from 15 PV patients and 15 healthy controls (HCs), the ratios of Th2/CD4+ T cells and Treg/CD4+ T cells, the activity of the mTOR pathway (PI3K/AKT/mTOR/p70S6K), the transcription factors and cytokines of Th2 and Treg cells were detected. Primary CD4+ T cells from PV patients were cultured under Th2- or Treg-polarizing conditions with or without rapamycin in vitro. We found that PV patients showed significantly elevated serum IL-4 when compared with HCs, and serum IL-4 level was positively correlated with the titer of anti-Dsg1/3 antibody and disease severity, while the serum TGF-β level was negatively correlated with the titer of anti-Dsg3 antibody and disease severity. Meanwhile, PV patients showed increased Th2/CD4+ T cell ratio; decreased Treg/CD4+ T cell ratio; elevated mRNA of PI3K, AKT, mTOR and protein of PI3K (P85), AKT, p-AKT (Ser473), mTOR, p-mTOR (Ser2448), p-p70S6K (Thr389), GATA3; reduced protein of forkhead box protein 3. Rapamycin inhibited Th2 cell differentiation and promoted Treg cell differentiation in vitro. These data suggest a close association between mTOR pathway activation and the loss of balance in Th2/Treg cells in peripheral blood of PV patients. Inhibiting mTORC1 can help restore the Th2/Treg balance.
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http://dx.doi.org/10.1093/abbs/gmab008DOI Listing
March 2021

Short-Term Intravenous Infusion of Cyclophosphamide in the Treatment of Refractory Pemphigus Vulgaris: A Retrospective Study.

Dermatology 2021 19;237(2):185-190. Epub 2020 Aug 19.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, China,

Background: Pemphigus is an autoimmune disease of the skin and mucous membranes. Glucocorticoids have been the most effective drug for the treatment of pemphigus; however, some patients are insensitive to glucocorticoid therapy. Cyclophosphamide has been extensively used in the treatment of pemphigus.

Objectives: To observe and evaluate the efficacy and safety of high-dose glucocorticoid with weekly intravenous cyclophosphamide in the treatment of refractory pemphigus vulgaris insensitive to glucocorticoids.

Methods: Clinical data of 19 patients with refractory pemphigus vulgaris (insensitive to glucocorticoid) who were treated with high-dose glucocorticoids(1.5 mg/kg/day prednisone) and weekly intravenous infusion of cyclophosphamide, and 24 patients who were sensitive to glucocorticoid therapy received a medium dose of glucocorticoid alone (1 mg/kg/day prednisone) were retrospectively analyzed.

Results: By the time the disease was brought under control, the average total dose of cyclophosphamide was 2.02 g. Comparison between the glucocorticoid-insensitive and glucocorticoid-sensitive groups showed that the average time to disease control was 2.68 vs. 2 weeks, and the average daily dosage of steroid was 1.33 ± 0.53 vs. 0.90 ± 0.28 mg/kg. At the 12- and 18-month follow-ups, the recurrence rate of the glucocorticoid-insensitive group was significantly lower than that of the sensitive group (5.3 vs. 37.5%, 15.8 vs. 45.8%). No serious adverse reactions were observed.

Conclusion: High-dose glucocorticoid plus weekly intravenous infusion of cyclophosphamide safely, effectively, and rapidly controlled the conditions of the patients with refractory pemphigus who were insensitive to glucocorticoids, shortened the duration of hospitalization, avoided the risk of complications that could be caused by further increasing the dose of glucocorticoids (>1.5 mg/kg/day), and lowered the recurrence rate within 18 months.
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http://dx.doi.org/10.1159/000508671DOI Listing
November 2021

Autoimmune Thyroid Disease in Patients with Systemic Lupus Erythematosus: A 7-year Retrospective Study in China.

Am J Med Sci 2018 10 30;356(4):344-349. Epub 2018 Jun 30.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China. Electronic address:

Background: The study was a retrospective case-controlled study. We aimed to determine the clinical and laboratory features of systemic lupus erythematosus (SLE) and compared the features of autoimmune thyroid disease (AITD) with those of SLE.

Materials And Methods: The study included 38 patients with SLE with AITD (SLE-AITD) and 190 age- and gender-matched SLE patients. The distribution of sociodemographic and clinical factors was compared between the SLE-AITD and SLE groups using Chi-square tests for gender and t tests for others. Univariate and multivariate logistic regression models were used to identify factors associated with the prevalence of AITD among SLE patients.

Results: In univariate analysis, malar rash, oral ulcers, serositis, anti-double-stranded DNA antibody positivity (anti-dsDNA+), anti-Sjögren's syndrome type A antibodies (SSA), anti-Sjögren's syndrome type B antibodies (SSB), low complement 3 (C3), and low complement 4 (C4) were significantly different between the SLE-AITD and SLE groups. There were no significant differences among other clinical or laboratory features. In multivariate analysis, serositis (adjusted odds ratio [AOR], 3.64; P = 0.00), anti-dsDNA+ (AOR, 0.30; P = 0.01) and low C3 (AOR, 0.30; P = 0.02) were all associated with SLE-AITD.

Conclusions: In our study, serositis was a risk factor for AITD, so we propose that AITD should be considered in lupus patients with serositis.
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http://dx.doi.org/10.1016/j.amjms.2018.06.022DOI Listing
October 2018

Lichenoid drug eruption in a child with Turner syndrome: A rare adverse reaction of recombinant human growth hormone.

Australas J Dermatol 2018 Nov 14;59(4):e311-e313. Epub 2018 Jun 14.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

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http://dx.doi.org/10.1111/ajd.12857DOI Listing
November 2018

Syphilis gastritis: a case report.

Int J STD AIDS 2018 06 4;29(7):723-725. Epub 2017 Jun 4.

1 Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

Awareness of the spectrum of clinical manifestations of syphilis, especially uncommon changes, is essential for diagnosis and effective management of patients. A 48-year-old Han businessman presented to the ear, nose and throat surgeons with an eight-week history of epigastric pain, a four-week history of a widespread non-itchy rash including the scrotal skin and a one-week history of tinnitus and dizziness. On examination, he was afebrile with widespread lymphadenopathy and a maculopapular rash affecting his trunk and scrotum. His abdomen was soft but tender in the epigastrium. The Treponema pallidum particle agglutination assay result was positive, and the rapid plasma reagin was 1:2. Gastroscopy showed ulcers in the gastric antrum and pylorus. Histopathological examination of gastric mucosa lesions showed a large amount of lymphoplasmacytic infiltrate detected in the lamina propria of the gastric mucosa. The T. pallidum Liferiver real time polymerase chain reaction kit assay performed on specimens from skin lesions and gastric mucosal tissue were positive. The patient was treated with intravenous sodium penicillin followed by intramuscular benzathine penicillin. On the fourth day of the treatment, the rash, epigastric pain and lymphadenopathy subsided. Two weeks after treatment, the tinnitus alleviated and vertigo disappeared.
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http://dx.doi.org/10.1177/0956462417711623DOI Listing
June 2018

Autologous peripheral blood haematopoietic stem cell transplantation for systemic lupus erythematosus: the observation of long-term outcomes in a Chinese centre.

Clin Exp Rheumatol 2017 May-Jun;35(3):500-507. Epub 2017 Mar 31.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Objectives: We aimed to evaluate the safety and long-term efficacy of autologous peripheral blood haematopoietic stem cell transplantation (APHSCT).

Methods: We did not want to evaluate the efficacy of antibodies but rather the clinical response by investigating progression-free survival and serologic response by assessing autoantibody titres and complement levels.

Results: Overall, 22 patients with SLE (17 females; median age, 23 years) undergoing APHSCT were included. The 3-year progression-free survival (PFS) was 77.27% at our centre. We found that all the patients survived over three years. The 5-year PFS and overall survival (OS) rate was 67.90% and 95.20%. The titres of antinuclear antibody (ANA), anti-double-stranded deoxyribonucleic acid antibody (anti-dsDNA), anti-Sm antibody, and 24-h urinary protein significantly decreased, while complements 3 (C3) and C4 normalised at 100 days after transplantation (p<0.05). Kidney re-biopsy revealed a decrease in immune complex deposits in patients with remission. The incidence of CMV reactivation was 59.09% after transplantation in 3 years. Pregnancy and childbirth were reported in three female patients after transplantation. The risk of post-transplantation complications persisted for many years.

Conclusions: Immunoablation followed by APHSCT has the potential to induce long-term clinical and serologic remissions despite withdrawal of immunosuppressive maintenance therapy. While relapses may occur, in our small cohort of patients we found no predictive markers for relapse development by analysing antibody and complement levels and urinary proteinuria.
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August 2017

Application of autologous hematopoietic stem cell transplantation for pemphigus.

Int J Dermatol 2017 Mar 17;56(3):296-301. Epub 2017 Jan 17.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Background: Pemphigus is a rare and fatal autoimmune disease for which the treatment options are limited. This study aimed to evaluate the efficacy of autologous peripheral hematopoietic stem cell transplantation (APHSCT) for pemphigus.

Methods: We conducted APHSCT for 12 pemphigus patients (seven males and five females, mean age 23.8 years) with life-threatening complications or who responded poorly to conventional therapy. Peripheral blood stem cells were mobilized with cyclophosphamide, granulocyte colony-stimulating factor, and rituximab, and purified autologous CD34 stem cells were infused. Overall survival rate, progression-free survival, and adverse events were recorded.

Results: With a mean follow-up period of 80.3 months, overall survival and complete clinical remission rates were 92% (11/12) and 75% (9/12), respectively. Adverse effects included pyrexia, allergy, infection, and elevation of enzymes. Only one patient died of severe sepsis and multiple organ failure 2 months after APHSCT.

Conclusion: Overall APHSCT is a promising therapeutic option for pemphigus.
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http://dx.doi.org/10.1111/ijd.13461DOI Listing
March 2017

Suppression of interleukin 17 contributes to the immunomodulatory effects of adipose-derived stem cells in a murine model of systemic lupus erythematosus.

Immunol Res 2016 12;64(5-6):1157-1167

Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People's Republic of China.

Due to roles in immunoregulation and low immunogenicity, mesenchymal stem cells have been suggested to be potent regulators of the immune response and may represent promising treatments for autoimmune disease. Adipose-derived stem cells (ADSCs), stromal cells derived from adipose tissue, were investigated with allogeneic ADSCs in B6.MRL/lpr mice, a murine model of systemic lupus erythematosus (SLE). We intravenously injected allogeneic ADSCs into SLE mice after disease onset and report that ADSCs reduced anti-ds DNA antibodies in serum and proteinuria in SLE mice. Also, ADSCs decreased IL-17 and IL-6 expression in serum of SLE mice. ADSCs alleviated renal damage and inflammatory cell infiltration and edema of the renal interstitium. Furthermore, ADSCs significantly downregulated renal IL-17 and CD68 expression, suggesting that ADSCs suppressed renal inflammation. ADSCs also decreased IL-17 mRNA expression and increased Foxp3, ROR-γt and miR-23b mRNA expression in renal tissue in SLE mice. ADSCs reduced renal protein expression of TAB 2 and IKK-α in SLE mice. Thus, ADSCs may be a novel potential therapy for treating SLE.
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http://dx.doi.org/10.1007/s12026-016-8866-yDOI Listing
December 2016

Hypertension in Malaysia: An Analysis of Trends From the National Surveys 1996 to 2011.

Medicine (Baltimore) 2016 Jan;95(2):e2417

From the International Medical University, Kuala Lumpur, Malaysia.

This study aimed to determine trends in prevalence, awareness, and control of hypertension in Malaysia and to assess the relationship between socioeconomic determinants and prevalence of hypertension in Malaysia.The distribution of hypertension in Malaysia was assessed based on available data in 3 National Health and Morbidity Surveys (NHMSs) and 1 large scale non-NHMS during the period of 1996 to 2011. Summary statistics was used to characterize the included surveys. Differences in prevalence, awareness, and control of hypertension between any 2 surveys were expressed as ratios. To assess the independent associations between the predictors and the outcome variables, regression analyses were employed with prevalence of hypertension as an outcome variable.Overall, there was a rising trend in the prevalence of hypertension in adults ≥30 years: 32.9% (30%-35.8%) in 1996, 42.6% (37.5%-43.5%) in 2006, and 43.5% (40.4%-46.6%) in 2011. There were significant increase of 32% from 1996 to 2011 (P < 0.001) and of 29% from 1996 to 2006 (P < 0.05), but only a small change of 1% from 2006 to 2011 (P = 0.6). For population ≥18 years, only a 1% increase in prevalence of hypertension occurred from the 2006 NHMS (32.2%) to the 2011 NHMS (32.7%) (P = 0.25). A relative increase of 13% occurred in those with primary education (P < 0.001) and a 15% increase was seen in those with secondary education (P < 0.001). The rate of increase in the prevalence of hypertension in the population with income level RM 3000-3999 was the highest (18%) during this period. In general, the older age group had higher prevalence of hypertension in the 2006 and 2011 NHMSs. The prevalence peaked at 74.1% among population aged 65 to 69 years in the 2011 NHMS. Both the proportion of awareness and the control of hypertension in Malaysia improved from 1996 to 2006. A change in the control of hypertension was 13% higher in women than in men.The findings suggest that the magnitude of hypertension in Malaysia needs additional attention. Strengthening the screening for hypertension in primary health-care settings in the high-risk groups and frequent health promotion to the community to enhance individual awareness and commitment to healthy living would be of immense value.
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http://dx.doi.org/10.1097/MD.0000000000002417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718248PMC
January 2016

[Expression of BATF, a member of the activator protein-1 family, in renal tissues of MRL/lpr mice].

Nan Fang Yi Ke Da Xue Xue Bao 2015 Jun;35(6):816-9

Department of dermatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. E-mail:

Objective: To investigate the expression of BATF, a member of the activator protein-1 family, in the renal tissues of mice with lupus nephritis.

Methods: The renal tissues from 24-week-old female MRL/lpr mice and age- and sex-matched C57BL/6 mice were examined for BATF protein expressions using Western blotting and for expressions of BATF, RORγt and IL-17A mRNA using quantitative real-time PCR. The results of laboratory examinations were analyzed in relation with the histopathology of the mice.

Results: The urinary protein and ds-DNA levels were significantly higher in MRL/lpr mice than in the control mice (P<0.05). Compared to normal control mice, MRL/lpr mice showed obvious glomerular fibrosis and inflammatory cell infiltrating with significantly increased BATF protein and mRNA expressions (P<0.05) and RORγt and IL-17 mRNA expressions in the renal tissues (P<0.05). In MRL/lpr mice, the expression of BATF mRNA was positively correlated with the RORγt and IL-17A mRNA expressions in the renal tissues.

Conclusion: The renal expressions of BATF protein and mRNA is increased in MRL/lpr mice. BATF may participate in the immunopathogenesis of lupus nephritis by enhancing Thl7 cell response.
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June 2015

A rapid and efficient method for primary culture of human adipose-derived stem cells.

Organogenesis 2013 Oct 22;9(4):287-95. Epub 2013 Nov 22.

Institute of Plastic Surgery; Affiliated Hospital of Guangdong Medical College; Zhanjiang, PR China.

Adipose tissue contains some populations, adipose-derived stem cells (ADSCs) which can differentiate into adipogenic, chondrogenic, osteogenic, myogenic, and endothelial cells. Furthermore, adipose tissue can be easily obtained in large quantities through a simple liposuction. ADSCs are thought to be an alternate source of autologous adult stem cells for cell-based therapy. However, it is time-consuming and inefficient to harvest ADSCs by using a traditional collagenase-digestion method. To meet the demand of large quantities of ADSCs in the basic and applied research of regenerative medicine, we developed a rapid and efficient method for isolation and culture of primary ADSCs. The results indicated that the ADSCs obtained with our method possessed strong abilities of proliferation and colony formation in vitro, and could keep low level of cell senescence with stable population doubling during long-term culture in vitro. Furthermore, these harvested ADSCs were capable to differentiate into osteogenic and adipogenic lineages in the specific induction medium. In addition, the results of flow cytometry analysis indicated that these ADSCs could positively express multiple CD markers, such as CD44, CD105, CD29, CD90, and CD13, and hardly expressed CD31, CD34, CD45, and CD106, which was homologous to the mesenchymal stem cells. Therefore, the ADSCs isolated with our method are consistent with previously reported characteristics of the ADSCs. This new method that we established in this study is an efficient tool to isolate and culture the stem cells from adipose tissue.
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http://dx.doi.org/10.4161/org.27153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903698PMC
October 2013

Allogeneic adipose-derived stem cells suppress Th17 lymphocytes in patients with active lupus in vitro.

Acta Biochim Biophys Sin (Shanghai) 2011 Oct 7;43(10):805-12. Epub 2011 Sep 7.

Department of Dermatology and Rheumatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Interleukin-17 (IL-17)-producing CD4(+) T cells (Th17 cells) have been proven to play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). To shed light on the mechanism of immunoregulation of adipose-derived stem cells (ADSCs), we investigated the effects of allogeneic ADSCs on the Th17 lymphocytes of patients with active SLE by co-culturing ADSCs and peripheral blood mononuclear cells of these patients in vitro. The results indicated that ADSCs from passage 3 (P3) down-regulated the proportion of Th17 cells and their abilities to produce IL-17, whereas ADSCs from passage 8 (P8) had contrasting effect. The results also showed cell-cell contact played a role in P3 down-regulation. Blocking the functional pathway of IL-23 (both its ligand and its receptor) also contributed to this suppression. These results suggested that immunomodulation of ADSCs may be achieved by partially suppressing the number and capability of Th17 lymphocytes, indicating that ADSCs could be employed as therapeutic tools for the autoimmune diseases.
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http://dx.doi.org/10.1093/abbs/gmr077DOI Listing
October 2011

Granulomatous skin infection caused by Malassezia pachydermatis in a dog owner.

Arch Dermatol 2006 Sep;142(9):1181-4

Department of Dermatology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524 001, China.

Background: Malassezia pachydermatis is part of the normal cutaneous microflora of dogs and many other mammals. M pachydermatis has not yet been reported as an agent that causes skin infection in humans, although it has been found to cause fungemia and other nosocomial infections in preterm newborns and immunocompromised adults.

Observations: Malassezia pachydermatis was isolated from the facial granuloma of a healthy woman and her dog's skin scrapings and cerumen. The yeast identity was established by standard methods and scanning electron microscopy. A skin biopsy specimen showed chronic inflammatory granuloma, numerous purple-red round or ovoid spores in the superficial necrotic tissue, and sparse red spores in the dermis. The skin lesions healed after oral fluconazole and cryotherapy.

Conclusions: Definite diagnosis of M pachydermatis-induced skin infection principally depends on the results of fungal culture and histologic examination, and the combination of oral fluconazole and adjunctive cryotherapy seems to be an effective therapeutic regimen.
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http://dx.doi.org/10.1001/archderm.142.9.1181DOI Listing
September 2006
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