Ameliorating effect of 2'-Fucosyllactose and 6'-Sialyllactose on lipopolysaccharide-induced intestinal inflammation.

Human milk oligosaccharides (HMO) affect gut microbiota during neonatal development, particularly with respect to the immune system. Bovine milk-based infant formulas have low oligosaccharide contents. Thus, efforts to fortify infant formulas with HMO are being undertaken. Two major HMO, 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL), exert anti-inflammatory effects; however, the associations between anti-inflammatory effects induced by 2'-FL and 6'-SL co-treatment and gut microbiota composition and metabolite modulation remain unclear. Therefore, in this study, we evaluated the effects of a mixture of these HMO. To determine the optimal HMO ratio for anti-inflammatory effects and elucidate its mode of action, LPS-induced inflammatory HT-29 epithelial cells and intestinal inflamed suckling mice were treated with various mixtures of 2'-FL and 6'-SL. 2'-FL:6'-SL ratio of 5:1 was identified as the most effective pre-treatment HMO mixture in vitro; thus, this ratio was selected and used for low, middle, and high-dose treatments for subsequent in vivo studies. In vivo, high-dose HMO treatment restored LPS-induced inflammation symptoms, such as body weight loss, colon length reduction, histological structural damage, and intestinal gene expression related to inflammatory responses. High-dose HMO was the only treatment that modulated the major phyla Bacteroidetes and Firmicutes and the genera Ihubacter, Mageeibacillus, and Saccharofermentans. These changes in microbial composition were correlated with intestinal inflammation-related gene expression and short-chain fatty acid production. To our knowledge, our study is the first to report the effects of Ihubacter, Mageeibacillus, and Saccharofermentans on short chain fatty acid levels, which can subsequently affect inflammatory cytokine and tight junction protein levels. Conclusively, the HMO mixture exerted anti-inflammatory effects through changes in microbiota and metabolite production. These findings suggested that supplementation of infant formula with HMO may benefit formula-fed infants by forming unique microbiota contributing to neonatal development.

Perioperative outcomes of laparoscopic low anterior resection using ArtiSential® versus robotic approach in patients with rectal cancer: a propensity score matching analysis.

BACKGROUND: Total mesorectal excision using conventional straight fixed devices may be technically difficult because of the narrow and concave pelvis. Several laparoscopic articulating tools have been introduced as an alternative to robotic systems. The aim of this study was to compare perioperative outcomes between laparoscopic low anterior resection using ArtiSential® and robot-assisted surgery for rectal cancer. METHODS: This retrospective study included 682 patients who underwent laparoscopic or robotic low anterior resection  for rectal cancer from September 2018 to December 2021. Among them, 82 underwent laparoscopic surgery using ArtiSential® (group A) and 201 underwent robotic surgery (group B). A total of 73 [group A; 66.37 ± 11.62; group B 65.79 ± 11.34] patients were selected for each group using a propensity score matching analysis. RESULTS: There was no significant difference in the baseline characteristics between group A and B. Mean operative time was longer in group B than A (163.5 ± 61.9 vs 250.1 ± 77.6 min, p < 0.001). Mean length of hospital stay was not significantly different between the two groups (6.2 ± 4.7 vs 6.7 ± 6.1 days, p = 0.617). Postoperative complications, reoperation, and readmission within 30 days after surgery were similar between the two groups. Pathological findings revealed that the circumferential resection margins were above 10 mm in both groups (11.00 ± 7.47 vs 10.17 ± 6.25 mm, p = 0.960). At least 12 lymph nodes were sufficiently harvested, with no significant difference in the number harvested between the groups (20.5 ± 9.9 vs 19.7 ± 7.3, p = 0.753). CONCLUSIONS: Laparoscopic low anterior resection using ArtiSential® can achieve acceptable clinical and oncologic outcomes. ArtiSential®, a multi-joint and articulating device, may serve a feasible alternative approach to robotic surgery in rectal cancer.

Improved diagnostic performance of susceptibility-weighted imaging with compressed sensing-sensitivity encoding and neuromelanin-sensitive MRI for Parkinson's disease and atypical Parkinsonism.

AIM: To verify the diagnostic performance of the loss of nigrosome-1 on susceptibility-weighted imaging (SWI) with compressed sensing-sensitivity encoding (CS-SENSE) and neuromelanin on neuromelanin-sensitive (NM) magnetic resonance imaging (MRI) for the diagnosis of Parkinson's disease (PD) and atypical Parkinsonism. MATERIALS AND METHODS: A total of 195 patients who underwent MRI between October 2019 and February 2020, including SWI, with or without CS-SENSE, and NM-MRI, were reviewed retrospectively. Two neuroradiologists assessed the loss of nigrosome-1 on SWI and neuromelanin on the NM-MRI. The result of N-3-fluoropropyl-2-beta-carbomethoxy-3-beta-(4-iodophenyl) nortropane positron-emission tomography (PET) was set as the reference standard. RESULTS: When CS-SENSE was applied for nigrosome-1 imaging on SWI, the non-diagnostic scan rate was lowered significantly from 19.3% (17/88) to 5.6% (6/107; p=0.004). Diagnosis of PD and atypical Parkinsonism based on the loss of nigrosome-1 on SWI and based on NM-MRI showed good diagnostic value (area under the curve [AUC] 0.821, 95% confidence interval [CI] = 0.755-0.875: AUC 0.832, 95% CI = 0.771-0.882, respectively) with a substantial inter-reader agreement (κ = 0.791 and 0.681, respectively). Combined SWI and neuromelanin had a similar discriminatory ability (AUC 0.830, 95% CI = 0.770-0.880). Similarly, the diagnosis of PD was excellent. CONCLUSIONS: CS-SENSE may add value to the diagnostic capability of nigrosome-1 on SWI to reduce the nondiagnostic scan rates. Furthermore, loss of nigrosome-1 on SWI or volume loss of neuromelanin on NM-MRI may be helpful for diagnosing PD.

Fungus isolated from dermatomycoses: a 9-month prospective study at Hospital Melaka.

INTRODUCTION: Dermatomycoses are common superficial cutaneous fungal infections which affect the skin, nails and human hairs. It affects 20 to 25% of the world population. The causative fungus varies geographically across the globe. Study on dermatomycoses is crucial to identify the aetiological fungus involved locally. The study aimed to determine the causative fungus of superficial fungal infections of the skin, nail and hair in patients presented to Hospital Melaka. METHODS: This was a prospective study conducted from 15th January 2022 till 15th October 2022 at Dermatology Clinic, Hospital Melaka. Subjects with clinical dermatomycoses were included in this study. The samples were collected from skin, nails and hairs clinically affected by tinea corporis/cruris/pedis, onychomycosis and tinea capitis respectively. A potassium hydroxide (KOH) study was performed on the sample in which the fungal hyphae/yeast positive subjects were sent for fungal culture and fungal PCR test. RESULT: A total of 222 clinical samples from skin, nails and hairs with a clinical suspicion of dermatomycoses yielded fungal hyphae/yeast in KOH. Majority of the samples were collected from skin (138, 62.2%), followed by nails (65, 29.3%) and hairs (19, 8.6%). Male to female ratio was 1.18: 1. The age ranged from 2 to 87 with the median of 55.5-yearsold. Out of 222 samples, 150 (67.6%) were fungal culture positive. From fungal culture positive samples, 87 samples were from tinea corporis, 50 samples were from onychomycoses and 13 samples were from tinea capitis. Trichophyton rubrum (39, 44.8%) was the commonest dermatophyte isolated in tinea corporis/cruris/pedis. Nondermatophyte moulds (NDM, 35, 70%) were the main fungi isolated in onychomycosis. Microsporum canis (7/53.8%) was the principal causative fungus among patients with tinea capitis. Among 150 fungal culture positive samples, 76 were fungal PCR positive. Only 38 samples consistently isolated same fungal species in both fungal culture and PCR test. CONCLUSION: Majority of tinea corporis and tinea capitis fungal culture isolated dermatophytes, especially Trichophyton rubrum and Microsporum canis, respectively. Non-dermatophyte moulds were mainly isolated in onychomycosis.

Severe cutaneous adverse reactions: A 5-year retrospective study at Hospital Melaka, Malaysia, from December 2014 to February 2020.

INTRODUCTION: Severe cutaneous adverse reactions (SCARs) are potentially lethal adverse drug reactions that involve the skin, mucous membranes, and internal organs, resulting in disability. SCARs include drug-induced epidermal necrolysis, which is Steven Johnson syndrome (SJS)/ Steven Johnson syndrome and toxic epidermal necrolysis overlap (SJS-TEN overlap)/ toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP), generalised bullous fixed drug eruption (GBFDE), and acute erythroderma. Awareness of local epidemiology of SCARs plays an important role in prescribing practices by healthcare provider. Recognition of SCARs enables the offending drug to be withdrawn immediately, which is the definitive treatment of SCARs. MATERIALS AND METHODS: This is a retrospective study reviewing SCAR cases reported to the Malaysian Adverse Drug Reactions Advisory Committee (MADRAC) registry at the Department of Dermatology, Hospital Melaka, for 5 years and 3 months from December 2014 to February 2020. RESULTS: A total of 41 SCARs cases were identified over the study duration. The incidence rate was 0.18%. All 41 cases require hospitalisations, with four cases (9.8%) managed in ICU and one mortality (2.4%) due to SJS-related complication. One patient had two episodes of SCARs. There were 22 male patients and 18 female patients. The majority were Malays (33, 80.5%), followed by Chinese (7, 17.1%) and Indonesian (1, 2.4%). There was no Indian patient with SCARs in this study. The mean age of patients was 47.2±17 years. Drug-induced epidermal necrolysis was the commonest type of SCARs (63.4%), and out of this, SJS accounted for the majority of cases (48.8%). Antibiotic was the main group of offending medication in this SCAR study (29.3%). The top five individual causative drugs of SCARs in sequence include allopurinol, phenytoin, carbamazepine, co-amoxiclav, and cephalexin. Allopurinol was the commonest culprit drug for drug-induced epidermal necrolysis and DRESS, phenytoin for acute erythroderma, and co-amoxiclav for AGEP. CONCLUSION: SJS was the most common manifestation and Allopurinol was the commonest culprit drug for SCAR cases in our cohort.

A Multistage Framework With Mean Subspace Computation and Recursive Feedback for Online Unsupervised Domain Adaptation.

In this paper, we address the Online Unsupervised Domain Adaptation (OUDA) problem and propose a novel multi-stage framework to solve real-world situations when the target data are unlabeled and arriving online sequentially in batches. Most of the traditional manifold-based methods on the OUDA problem focus on transforming each arriving target data to the source domain without sufficiently considering the temporal coherency and accumulative statistics among the arriving target data. In order to project the data from the source and the target domains to a common subspace and manipulate the projected data in real-time, our proposed framework institutes a novel method, called an Incremental Computation of Mean-Subspace (ICMS) technique, which computes an approximation of mean-target subspace on a Grassmann manifold and is proven to be a close approximate to the Karcher mean. Furthermore, the transformation matrix computed from the mean-target subspace is applied to the next target data in the recursive-feedback stage, aligning the target data closer to the source domain. The computation of transformation matrix and the prediction of next-target subspace leverage the performance of the recursive-feedback stage by considering the cumulative temporal dependency among the flow of the target subspace on the Grassmann manifold. The labels of the transformed target data are predicted by the pre-trained source classifier, then the classifier is updated by the transformed data and predicted labels. Extensive experiments on six datasets were conducted to investigate in depth the effect and contribution of each stage in our proposed framework and its performance over previous approaches in terms of classification accuracy and computational speed. In addition, the experiments on traditional manifold-based learning models and neural-network-based learning models demonstrated the applicability of our proposed framework for various types of learning models.

Characteristics and quality of life in pemphigus patients.

INTRODUCTION: Pemphigus is an autoimmune blistering disease affecting the skin and mucus membranes. It is a debilitating skin condition with painful bullae and erosions, which may limit the patient's daily activities. Therefore, measuring the quality of life (QoL) from the perspective of physical, functional, social, and emotional well-being is important to address the disease burden. This study aims to review the demography and assess the impact of disease on QoL in pemphigus patients at the Department of Dermatology, Hospital Melaka. MATERIALS AND METHODS: This is a single-centre, crosssectional study on the characteristics and QoL among the pemphigus patients at the Department of Dermatology, Melaka General Hospital, from August 2020 to July 2021. Patients' information was collected, and each patient was assessed objectively on the disease severity physically using the Pemphigus Disease Area Index (PDAI) scoring system. The disease severity was then assessed subjectively, in which each participant was given three questionnaires to answer, namely the Dermatology Life Quality Index (DLQI), Visual Analogue Scale (VAS) for pain and itch, and Autoimmune Bullous Disease Quality of Life (ABQOL). RESULTS: There were a total of 30 pemphigus patients (13 males, 17 females), with an average age of 54.0 ± 13.6 years. Our study population had low median PDAI score (2.0 ± 4.0) with low median DLQI (3.0 ± 8.0) and ABQOL (11.0 ± 12.0). The median VAS scores for pain (1.0 ± 2.0) and itch (2.0 ± 3.0) were also low. Patients with tertiary educational qualification reported higher median DLQI (10.0 ± 12.0, p = 0.016) and ABQOL (21.0 ± 23.0, p = 0.026). Significant correlation was neither observed between PDAI and DLQI scores nor observed between PDAI and ABQOL scores. The DLQI and ABQOL scores were not affected by gender, age, ethnicity, and duration of illness. CONCLUSION: Most of the patients in our study cohort had low DLQI and ABQOL scores, with mild clinical severity, as evidenced by low PDAI and VAS scores for both pain and itch. Disease severity had no correlation with QoL in our study. However, educational level showed significant influence on the QoL.

Mid-treatment Fluorodeoxyglucose Positron Emission Tomography in Human Papillomavirus-related Oropharyngeal Squamous Cell Carcinoma Treated with Primary Radiotherapy: Nodal Metabolic Response Rate can Predict Treatment Outcomes.

AIMS: To evaluate whether biomarkers derived from fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) performed prior to (prePET) and during the third week (interim PET; iPET) of radiotherapy can predict treatment outcomes in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPC). MATERIALS AND METHODS: This retrospective analysis included 46 patients with newly diagnosed OPC treated with definitive (chemo)radiation and all patients had confirmed positive HPV status (HPV+OPC) based on p16 immunohistochemistry. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of primary, index node (node with the highest TLG) and total lymph nodes and their median percentage (≥50%) reductions in iPET were analysed, and correlated with 5-year Kaplan-Meier and multivariable analyses (smoking, T4, N2b-3 and AJCC stage IV), including local failure-free survival, regional failure-free survival, locoregional failure-free survival (LRFFS), distant metastatic failure-free survival (DMFFS), disease-free survival (DFS) and overall survival. RESULTS: There was no association of outcomes with prePET parameters observed on multivariate analysis. A complete metabolic response of primary tumour was seen in 13 patients; the negative predictive value for local failure was 100%. More than a 50% reduction in total nodal MTV provided the best predictor of outcomes, including LRFFS (88% versus 47.1%, P = 0.006, hazard ratio = 0.153) and DFS (78.2% versus 41.2%, P = 0.01, hazard ratio = 0.234). More than a 50% reduction in index node TLG was inversely related to DMFFS: a better nodal response was associated with a higher incidence of distant metastatic failure (66.7% versus 100%, P = 0.009, hazard ratio = 3.0). CONCLUSION: The reduction (≥50%) of volumetric nodal metabolic burden can potentially identify a subgroup of HPV+OPC patients at low risk of locoregional failure but inversely at higher risk of distant metastatic failure and may have a role in individualised adaptive radiotherapy and systemic therapy.

Association between autophagy and KRAS mutation with clinicopathological variables in colorectal cancer patients.

Autophagy is a host defensive mechanism responsible for eliminating harmful cellular components through lysosomal degradation. Autophagy has been known to either promote or suppress various cancers including colorectal cancer (CRC). KRAS mutation serves as an important predictive marker for epidermal growth factor receptor (EGFR)-targeted therapies in CRC. However, the relationship between autophagy and KRAS mutation in CRC is not well-studied. In this single-centre study, 92 formalin-fixed paraffin-embedded (FFPE) tissues of CRC patients (42 Malaysian Chinese and 50 Indonesian) were collected and KRAS mutational status was determined by quantitative PCR (qPCR) (n=92) while the expression of autophagy effector (p62, LC3A and LC3B) was examined by immunohistochemistry (IHC) (n=48). The outcomes of each were then associated with the clinicopathological variables (n=48). Our findings demonstrated that the female CRC patients have a higher tendency in developing KRAS mutation in the Malaysian Chinese population (p<0.05). Expression of autophagy effector LC3A was highly associated with the tumour grade in CRC (p<0.001) but not with other clinicopathological parameters. Lastly, the survival analysis did not yield a statistically significant outcome. Overall, this small cohort study concluded that KRAS mutation and autophagy effectors are not good prognostic markers for CRC patients.

Lactobacillus-fermented milk products attenuate bone loss in an experimental rat model of ovariectomy-induced post-menopausal primary osteoporosis.

AIM: In this study, we investigated the anti-osteoporotic effect of two fermented milk products (FMPs) fermented by Lactobacillus plantarum A41 and Lactobacillus fermentum SRK414 on a rat model of ovariectomy-induced post-menopausal primary osteoporosis. METHODS AND RESULTS: The two Lactobacillus FMPs increased the bone volume and bone mineral density (BMD) in ovariectomized (OVX) rats, and normalized the bone biomarkers in the serum. Additionally, they altered the gene expression levels of bone-metabolism-related markers. Furthermore, the two Lactobacillus FMPs downregulated bone-apoptosis-related genes stimulated by ovariectomy. Interestingly, the Lactobacillus FMPs decreased the levels of inflammation markers in the serum, bone, ileum and colon of the rats. Gut bacterial populations were also affected upon FMP treatment due to increase in the abundance of the genus Lactobacillus and Faecalibacterium prausnitzii. CONCLUSIONS: Milk products fermented by L. plantarum A41 and L. fermentum SRK414 can exhibit anti-osteoporotic effects on post-menopausal osteoporosis via regulating the expression of bone-metabolism-related markers. SIGNIFICANCE AND IMPACT OF THE STUDY: The two Lactobacillus FMPs used in the study can be an ideal method that has its potential of treating post-menopausal osteoporosis instead of drug treatments.

Mapping of a New Deformation Region around

We performed the first direct mass measurements of neutron-rich scandium, titanium, and vanadium isotopes around the neutron number 40 at the RIKEN RI Beam Factory using the time-of-flight magnetic-rigidity technique. The atomic mass excesses of ^{58-60}Sc, ^{60-62}Ti, and ^{62-64}V were measured for the first time. The experimental results show that the two-neutron separation energies in the vicinity of ^{62}Ti increase compared to neighboring nuclei. This shows that the masses of Ti isotopes near N=40 are affected by the Jahn-Teller effect. Therefore, a development of Jahn-Teller stabilization appears below the Cr isotopes, and the systematics in Sc, Ti, and V isotopes suggest that ^{62}Ti is located close to the peak of the Jahn-Teller effect.

How Different is the Core of

The structure of a neutron-rich ^{25}F nucleus is investigated by a quasifree (p,2p) knockout reaction at 270A MeV in inverse kinematics. The sum of spectroscopic factors of π0d_{5/2} orbital is found to be 1.0±0.3. However, the spectroscopic factor with residual ^{24}O nucleus being in the ground state is found to be only 0.36±0.13, while those in the excited state is 0.65±0.25. The result shows that the ^{24}O core of ^{25}F nucleus significantly differs from a free ^{24}O nucleus, and the core consists of ∼35% ^{24}O_{g.s.}. and ∼65% excited ^{24}O. The result may infer that the addition of the 0d_{5/2} proton considerably changes neutron structure in ^{25}F from that in ^{24}O, which could be a possible mechanism responsible for the oxygen dripline anomaly.

A Two-Stage Approach to Few-Shot Learning for Image Recognition.

This paper proposes a multi-layer neural network structure for few-shot image recognition of novel categories. The proposed multi-layer neural network architecture encodes transferable knowledge extracted from a large annotated dataset of base categories. This architecture is then applied to novel categories containing only a few samples. The transfer of knowledge is carried out at the feature-extraction and the classification levels distributed across the two training stages. In the first-training stage, we introduce the relative feature to capture the structure of the data as well as obtain a low-dimensional discriminative space. Secondly, we account for the variable variance of different categories by using a network to predict the variance of each class. Classification is then performed by computing the Mahalanobis distance to the mean-class representation in contrast to previous approaches that used the Euclidean distance. In the second-training stage, a category-agnostic mapping is learned from the mean-sample representation to its corresponding class-prototype representation. This is because the mean-sample representation may not accurately represent the novel category prototype. Finally, we evaluate the proposed network structure on four standard few-shot image recognition datasets, where our proposed few-shot learning system produces competitive performance compared to previous work. We also extensively studied and analyzed the contribution of each component of our proposed framework.

Protopanaxatriol inhibits melanin synthesis through inactivation of the pCREB-MITF-tyrosinase signalling pathway in melanocytes.

Ginsenosides are major active components of ginseng, and have diverse pharmacological properties in traditional medicine. Recent reports have shown that ginsenosides modify skin physiology and mitigate skin disorders such as photoageing and hyperpigmentation. We evaluated the antimelanogenic efficacy of protopanaxatriol, a major category of ginsenosides, as a depigmenting agent. Protopanaxatriol significantly reduced intracellular and extracellular melanin content in a concentration-dependent manner in B16 melanoma cells treated with α-melanocyte-stimulating hormone. In normal human epidermal melanocytes, protopanaxatriol clearly decreased melanin synthesis and dendrite elongation. In addition, protopanaxatriol dramatically suppressed the expression of genes encoding the melanogenic proteins tyrosinase, tyrosinase-related protein-1 and -2, and microphthalmia-associated transcription factor through dephosphorylation of cAMP response element-binding protein. These results suggest that protopanaxatriol could be an effective candidate anti-melanogenic agent.

Extraction of the Landau-Migdal Parameter from the Gamow-Teller Giant Resonance in

The key parameter to discuss the possibility of the pion condensation in nuclear matter, i.e., the so-called Landau-Migdal parameter g^{'}, was extracted by measuring the double-differential cross sections for the (p,n) reaction at 216 MeV/u on a neutron-rich doubly magic unstable nucleus, ^{132}Sn with the quality comparable to data taken with stable nuclei. The extracted strengths for Gamow-Teller (GT) transitions from ^{132}Sn leading to ^{132}Sb exhibit the GT giant resonance (GTR) at the excitation energy of 16.3±0.4(stat)±0.4(syst) MeV with the width of Γ=4.7±0.8 MeV. The integrated GT strength up to E_{x}=25 MeV is S_{GT}^{-}=53±5(stat)_{-10}^{+11}(syst), corresponding to 56% of Ikeda's sum rule of 3(N-Z)=96. The present result accurately constrains the Landau-Migdal parameter as g^{'}=0.68±0.07, thanks to the high sensitivity of the GTR energy to g^{'}. In combination with previous studies on the GTR for ^{90}Zr and ^{208}Pb, the result of this work shows the constancy of this parameter in the nuclear chart region with (N-Z)/A=0.11 to 0.24 and A=90 to 208.

Magic Nature of Neutrons in

We perform the first direct mass measurements of neutron-rich calcium isotopes beyond neutron number 34 at the RIKEN Radioactive Isotope Beam Factory by using the time-of-flight magnetic-rigidity technique. The atomic mass excesses of ^{55-57}Ca are determined for the first time to be -18650(160), -13510(250), and -7370(990) keV, respectively. We examine the emergence of neutron magicity at N=34 based on the new atomic masses. The new masses provide experimental evidence for the appearance of a sizable energy gap between the neutron 2p_{1/2} and 1f_{5/2} orbitals in ^{54}Ca, comparable to the gap between the neutron 2p_{3/2} and 2p_{1/2} orbitals in ^{52}Ca. For the ^{56}Ca nucleus, an open-shell property in neutrons is suggested.

Depigmentation efficacy of galacturonic acid through tyrosinase regulation in B16 murine melanoma cells and a three-dimensional human skin equivalent.

Sugar is a well-known cosmetic ingredient for moisturizing skin with minimal side-effects. Several reports have demonstrated an antimelanogenic effect of sugar in melanocytes. We evaluated the whitening efficacy of galacturonic acid (GA), the main component of pectin, as an anti-melanogenic agent. GA significantly suppressed melanin synthesis and secretion in a concentration-dependent manner in α-melanocyte stimulating hormone-treated B16 melanoma cells, and inhibited tyrosinase activity and expression at a dose of 10 mmol/L. In a three-dimensional human skin equivalent (MelanoDerm), GA clearly brightened tissue colour. Haematoxylin and eosin and Fontana-Masson (F&M) staining of tissue sections revealed decreased melanin production without skin tissue collapse in the presence of GA. Interestingly, GA dramatically suppressed gene expression of the melanogenic proteins tyrosinase, tyrosinase-related protein (TYRP)-1 and microphthalmia-associated transcription factor, but not TYRP-2. The results support the utility of GA as an effective candidate antimelanogenic agent.

Viral activity and outcome of hepatitis B surface antigen-positive grafts in deceased liver transplantation.

Indications of liver transplantation are extensive, but deceased donation does not meet the demand. Hepatitis B surface antigen (HBsAg)-positive grafts used to be discarded in the past. The aim of this study was to examine viral activity and outcome of HBsAg-positive deceased grafts transplanted to HBsAg-positive recipients. Eleven HBsAg-positive deceased grafts were transplanted to HBsAg-positive patients with acute liver failure (3 patients), hepatocellular carcinoma (6 patients) and repeatedly bleeding varices (2 patients). Postoperatively, hepatitis B virus (HBV) infection was treated by a combination of antiviral nucleoside and nucleotide analogues. HBV DNA and HBsAg were measured periodically. The median (interquartile) model of end-stage liver disease score for the recipients was 19 (16-32) with a range from 11 to 40. HBV DNA was detected in 6 patients with a range from 61 to 1083 IU/mL before transplantation. After transplantation, HBV DNA was detected in 4 patients in the first month and 2 patients in the 6th month and became undetectable for all patients at end of the first year. The quantitative HBsAg ranged from 0.86 to 241.1 IU/mL at 6 months and 0.34 to 238.5 IU/mL at 24 months (P = .135). Three of the patients died in the early phase, and the other patients were followed up for 40.0 ± 19.2 months with normal liver function. In conclusion, HBsAg-positive deceased liver grafts function well with minimal viral activity under treatment of combined antiviral nucleoside and nucleotide analogues. Use of HBsAg-positive deceased grafts is feasible and increases the donor pool to rescue dying patients.