Three Undescribed Iridoid Derivatives Isolated from the Fruits of Vitex trifolia with Their Cytotoxic and Antimicrobial Activities.

Vitex trifolia L. is a medicinal plant and widely distributed in the northern mountainous areas of Vietnam. Phytochemical study on the fruits of this plant led to the isolation of nine iridoid derivatives (1-9) including three undescribed compounds (1-3). Their structures were elucidated to be 3''-hydroxyscrophuloside A1 (1), 3''-hydroxycallicoside D (2), 2'-p-hydroxybenzoylaucubin (3), 6'-p-hydroxybenzoylmussaenosidic acid (4), nishindaside (5), agnuside (6), 10-O-vanilloylaucubin (7), 6'-O-p-hydroxybenzoyl-gardoside (8), and buddlejoside B (9) based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1, 2, 4, and 8 significantly posessed anti-barterial activity against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa strains with MIC values in range of 16-64 µg/mL. At concentration of 20 µM, compounds 1-9 did not show cytotoxic effects against human lung cancer cells (PC9).

The Medical Outcome Study Social Support Survey (MOS-SSS): A psychometric systematic review.

AIMS: To evaluate and synthesize psychometric properties of the MOS-SSS and to identify quality versions of MOS-SSS for use in future research and practice. DESIGN: A psychometric systematic review. DATA SOURCES: Articles about the translation, adaptation, or validation of the MOS-SSS in Medline, PubMed, CINAHL, and Web of Science and their reference lists published before 11 November 2022. REVIEW METHODS: The review followed the Consensus Standards for the Selection of Health Measurement Instruments guidelines. RESULTS: The review included 35 articles. Eleven versions of MOS-SSS (3, 4, 5, 6, 8, 12, 13, 16, 18, 19, and 22 items) have been validated in various populations and 13 languages. Of 14 studies developing a translated version of MOS-SSS, four studies performed both an experts' evaluation of content validity and a face validity test; two studies reported translation evaluation in the form of a content validity index. Of 35 studies, six performed both exploratory factor analysis and confirmatory factor analysis for structural validity; hypotheses and measurements for construct validity testings were often not clearly stated; two examined criterion validity; and four assessed cross-cultural validity. Internal consistency reliabilities were commonly examined by calculating Cronbach's alpha and reported satisfactory. Five studies analysed test-retest reliabilities using intra correlation coefficient. Methodological concerns exist. CONCLUSION: The English 19-item, Farsi Persian 19-item, and Vietnamese 19-item versions are recommended for future use in research and practice. Italian 19-item and Malaysian 13-item versions are not recommended to be used in future research and practice. All other versions considered in this review have potential use in future research and practice. Proper procedures for developing a translated version of MOS-SSS and validating the scale are recommended. IMPACT: The review identified quality versions of MOS-SSS to measure social support in future research and practice. The study also indicated methodological issues in current validation studies. Application of the study findings and recommendations can be useful to improve outcome measurement quality and maximize the efficiency of resource use in future research and practice. NO PATIENT OR PUBLIC CONTRIBUTION: This systematic review synthesized the evidence from previous research and did not involve any human participation.

Self-report instruments for measuring patient dignity: A psychometric systematic review.

AIMS: To synthesize and evaluate the psychometric properties of self-report instruments that measure patient dignity. DESIGN: A psychometric systematic review. DATA SOURCES: A comprehensive search of studies published from inception until February 17, 2022, was performed using PubMed, Embase, CINAHL, Web of Science, and Scopus. REVIEW METHODS: The methodological quality of the psychometric studies was evaluated following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines. RESULTS: Eleven self-report instruments that evaluate dignity were identified. For most instruments, psychometric properties, including reliability, cross-cultural validity, responsiveness, and measurement error, had not been adequately examined. The Patient Dignity Inventory (PDI), the Jacelon's Attributed Dignity Scale (JADS), and the Inpatient Dignity Scale (IPDS) had acceptable content validity, structure validity, and internal consistency to measure dignity among adult patients under palliative care, community-dwelling older adults, and inpatients receiving daily care. CONCLUSION: The PDI, the JADS, and the IPDS are recommended for future clinical practice and research to measure dignity among adult patients under palliative care, community-dwelling older adults, and inpatients receiving daily care. Early identification of patients' dignity-related problems in nursing care can prevent negative health outcomes and help develop a timely intervention to promote patients' health and recovery. IMPACT: Given that the psychometric properties of the existing self-report dignity instruments have not been systematically assessed, the present review utilized comprehensive methods according to COSMIN to evaluate and determine the most appropriate measure for research and practice. The PDI, the JADS, and the IPDS demonstrated satisfactory psychometric properties and are, thus, recommended for clinical and research applications. Nursing professionals can employ these instruments to assess and promptly identify dignity issues among both young and older adults in hospitals and communities.

Specific localization of nesprin-1-α2, the short isoform of nesprin-1 with a KASH domain, in developing, fetal and regenerating muscle, using a new monoclonal antibody.

BACKGROUND: Nesprin-1-giant (1008kD) is a protein of the outer nuclear membrane that links nuclei to the actin cytoskeleton via amino-terminal calponin homology domains. The short nesprin-1 isoform, nesprin-1-α2, is present only in skeletal and cardiac muscle and several pathogenic mutations occur within it, but the functions of this short isoform without calponin homology domains are unclear. The aim of this study was to determine mRNA levels and protein localization of nesprin-1-α2 at different stages of muscle development in order to shed light on its functions. RESULTS: mRNA levels of all known nesprin-1 isoforms with a KASH domain were determined by quantitative PCR. The mRNA for the 111 kD muscle-specific short isoform, nesprin-1-α2, was not detected in pre-differentiation human myoblasts but was present at significant levels in multinucleate myotubes. We developed a monoclonal antibody against the unique amino-terminal sequence of nesprin-1-α2, enabling specific immunolocalization for the first time. Nesprin-1-α2 protein was undetectable in pre-differentiation myoblasts but appeared at the nuclear rim in post-mitotic, multinucleate myotubes and reached its highest levels in fetal muscle. In muscle from a Duchenne muscular dystrophy biopsy, nesprin-1-α2 protein was detected mainly in regenerating fibres expressing neonatal myosin. Nesprin-1-giant was present at all developmental stages, but was also highest in fetal and regenerating fibres. In fetal muscle, both isoforms were present in the cytoplasm, as well as at the nuclear rim. A pathogenic early stop codon (E7854X) in nesprin-1 caused reduced mRNA levels and loss of protein levels of both nesprin-1-giant and (unexpectedly) nesprin-1-α2, but did not affect myogenesis in vitro. CONCLUSIONS: Nesprin-1-α2 mRNA and protein expression is switched on during myogenesis, alongside other known markers of muscle differentiation. The results show that nesprin-1-α2 is dynamically controlled and may be involved in some process occurring during early myofibre formation, such as re-positioning of nuclei.

Discovery of new triterpene glycosides from Dendrobium officinale with their α-glucosidase and α-amylase inhibitory activity.

In this study, seven new pentacyclic triterpene glycosides, named dendrocinaosides A-G (1-7), and six known ones (8-13) were isolated from the whole plants of Dendrobium officinale. Their structures were determined by analyses of HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1-4, 8, and 9 potentially inhibited α-glucosidase and α-amylase activities with the IC50 values ranging from 31.3 ± 2.2 to 42.4 ± 2.5 µM for anti α-glucosidase and from 36.5 ± 1.8 to 56.4 ± 2.0 µM for anti α-amylase activities, respectively, which were lower than that of the positive control, acarbose, showing IC50 values of 47.1 ± 1.4 µM for anti α-glucosidase and 145.7 ± 2.2 µM for anti α-amylase.

The gemin2-binding site on SMN protein: accessibility to antibody.

Reduced levels of SMN (survival-of-motor-neurons) protein are the cause of spinal muscular atrophy, an inherited disorder characterised by loss of motor neurons in early childhood. SMN associates with more than eight other proteins to form an RNA-binding complex involved in assembly of the spliceosome. Two monoclonal antibodies (mAbs), MANSMA1 and MANSMA12, have been widely-used in studies of SMN function and their precise binding sites on SMN have now been identified using a phage-displayed peptide library. The amino-acid residues in SMN required for antibody binding are the same as the five most important contact residues for interaction with gemin2. MANSMA12 immuno-precipitated SMN and gemin2 from HeLa cell extracts as efficiently as mAbs against other SMN epitopes or against gemin2. We explain this by showing that SMN exists as large multimeric complexes. This SMN epitope is highly-conserved and identical in human and mouse. To explain the vigorous immune response when mice are immunised with recombinant SMN alone, we suggest this region is masked by gemin2, or a related protein, throughout development, preventing its recognition as a "self-antigen". The epitope for a third mAb, MANSMA3, has been located to eight amino-acids in the proline-rich domain of SMN.

Detection of the dystroglycanopathy protein, fukutin, using a new panel of site-specific monoclonal antibodies.

Mutations in the gene encoding fukutin protein cause Fukuyama muscular dystrophy, a severe congenital disorder that occurs mainly in Japan. A major consequence of the mutation is reduced glycosylation of alpha-dystroglycan, which is also a feature of other forms of congenital and limb-girdle muscular dystrophy. Immunodetection of endogenous fukutin in cells and tissues has been difficult and this has hampered progress in understanding fukutin function and disease pathogenesis. Using a new panel of monoclonal antibodies which bind to different defined sites on the fukutin molecule, we now show that fukutin has the predicted size for a protein without extensive glycosylation and is present at the Golgi apparatus at very low levels. These antibodies should enable more rapid future progress in understanding the molecular function of fukutin.

Elevated trauma exposure and mental health burden among men who have sex with men in Vietnam.

The purpose of this study was to characterize trauma exposure and mental health burden among men who have sex with men (MSM) in Hanoi, Vietnam. Participants comprise 100 HIV-positive and 98 high-risk, HIV-negative MSM, ranging from 18 to 29 years of age. Data were collected using the Childhood Trauma Questionnaire, Traumatic Events Inventory, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and PTSD Symptom Scale. A subset of participants (n = 12) were also interviewed to evaluate community perception of the prevalence, causation, and available treatment options for mental health issues within the MSM community in Vietnam. In our sample, 23.2% reported having experienced moderate-to-severe childhood physical abuse; 18.7% physical neglect; 13.6% emotional abuse; 11.1% emotional neglect; and 26.8% sexual abuse. Such trauma exposure continued into adulthood and manifested most commonly in the form of interpersonal violence. Approximately 37.4% of the sample met the criteria for probable PTSD; 26.8% for moderate-to-severe depression; and 20.2% for moderate-to-severe anxiety. Neither exposure nor mental health burden differed by serostatus. Linear regression revealed that childhood emotional abuse was the only sub-type of trauma significantly associated with depression, anxiety, and PTSD symptoms. The majority of interviewees believed that mental health burden was higher among MSM relative to the general population and attributed this to their vulnerability to interpersonal violence and lack of available coping resources. However, few believed that these mental health issues warranted clinical attention, and only one participant was able to identify a mental health service provider. Our findings suggest that trauma exposure and mental health burden are prevalent among MSM, irrespective of serostatus, and much higher than what has been previously reported among the general population in Vietnam.

The mouse mismatch repair protein, MSH3, is a nucleoplasmic protein that aggregates into denser nuclear bodies under conditions of stress.

The mismatch repair protein, MSH3, together with MSH2, forms the MutSß heterodimer which recognizes and repairs base pair mismatches and larger insertion/deletion loops in DNA. Lack of specific antibodies against mouse MSH3 has hampered studies of its expression and localization. Mouse MSH3 is not immunogenic in normal mice. This problem was overcome by immunizing msh3-knockout mice and generating a panel of ten monoclonal antibodies, two of which localize MSH3 specifically in cultured mouse cells and bind to an epitope containing amino-acids 33-37. The panel also includes two antibodies that recognise both mouse and human MSH3 and bind to a conserved epitope containing amino-acids 187-194. The mouse MSH3-specific antibodies show that MSH3 is a nuclear protein with a finely-granular nucleoplasmic distribution, largely absent from areas of condensed heterochromatin. Specificity of the localization was demonstrated by absence of immunostaining in a cell line from the msh3-knockout mouse. Furthermore, we show for the first time that stress treatment of mouse cells with ethanol or hydrogen peroxide caused the re-distribution of MSH3 into nuclear bodies containing the proliferating cell nuclear antigen (PCNA), a known binding partner of MutSß.

Nesprin-2 epsilon: a novel nesprin isoform expressed in human ovary and Ntera-2 cells.

The nuclear envelope-associated cytoskeletal protein, nesprin-2, is encoded by a large gene containing several internal promoters that produce shorter isoforms. In a study of Ntera-2 teratocarcinoma cells, a novel isoform, nesprin-2-epsilon, was found to be the major mRNA and protein product of the nesprin-2 gene. Its existence was predicted by bioinformatic analysis, but this is the first direct demonstration of both the mRNA and the 120 kDa protein which is located at the nuclear envelope. In a panel of 21 adult and foetal human tissues, the nesprin-2-epsilon mRNA was strongly expressed in ovary but was a minor isoform elsewhere. The expression pattern suggests a possible link with very early development and a likely physiological role in ovary.

Nesprins, but not sun proteins, switch isoforms at the nuclear envelope during muscle development.

Nesprins are a family of nuclear transmembrane proteins anchored via Sun proteins to the nuclear membrane. Analysis of nesprins during human muscle development revealed an increase in nesprin-1-giant during early myogenesis in vitro. During the transition from immature to mature muscle fibres in vivo, nesprin-2 partly replaced nesprin-1 at the nuclear envelope and short nesprin isoforms became dominant. Sun1 and Sun2 proteins remained unchanged during this fibre maturation. In emerin-negative skin fibroblasts, nesprin-2-giant was relocated from the nuclear envelope to the cytoplasm, not to the endoplasmic reticulum, while nesprin-1 remained at the nuclear envelope. In emerin-negative keratinocytes lacking nesprin-1, nesprin-2 remained at the nuclear envelope. HeLa cell nuclear envelopes lacked nesprin-1, which was the dominant form in myoblasts, while a novel 130-kD nesprin-2 isoform dominated Ntera-2 cells. The results suggest the possibility of isoform-specific and tissue-specific roles for nesprins in nuclear positioning.

Pharmacological Properties, Volatile Organic Compounds, and Genome Sequences of Bacterial Endophytes from the Mangrove Plant Rhizophora apiculata Blume.

Mangrove plant endophytic bacteria are prolific sources of bioactive secondary metabolites. In the present study, twenty-three endophytic bacteria were isolated from the fresh roots of the mangrove plant Rhizophora apiculata. The identification of isolates by 16S rRNA gene sequences revealed that the isolated endophytic bacteria belonged to nine genera, including Streptomyces, Bacillus, Pseudovibrio, Microbacterium, Brevibacterium, Microbulbifer, Micrococcus, Rossellomorea, and Paracoccus. The ethyl acetate extracts of the endophytic bacteria's pharmacological properties were evaluated in vitro, including antimicrobial, antioxidant, α-amylase and α-glucosidase inhibitory, xanthine oxidase inhibitory, and cytotoxic activities. Gas chromatography-mass spectrometry (GC-MS) analyses of three high bioactive strains Bacillus sp. RAR_GA_16, Rossellomorea vietnamensis RAR_WA_32, and Bacillus sp. RAR_M1_44 identified major volatile organic compounds (VOCs) in their ethyl acetate extracts. Genome analyses identified biosynthesis gene clusters (BGCs) of secondary metabolites of the bacterial endophytes. The obtained results reveal that the endophytic bacteria from R. apiculata may be a potential source of pharmacological secondary metabolites, and further investigations of the high bioactive strains-such as fermentation and isolation of pure bioactive compounds, and heterologous expression of novel BGCs in appropriate expression hosts-may allow exploring and exploiting the promising bioactive compounds for future drug development.

Mental health in HIV prevention and care: A qualitative study of challenges and facilitators to integration in Vietnam.

INTRODUCTION: Globally, men who have sex with men (MSM) experience a disproportionate burden of mental health issues. While HIV service providers may possess the skills and relationships to provision mental health and psychosocial support (MHPSS) to this population, task-sharing models that integrate MHPSS into HIV contexts remain limited. The aim of this study was to explore the sociodemographic, psychological, and structural factors operant at the client and HIV service provider levels that shape MHPSS access and burden among MSM and opportunities for integration in Vietnam. METHODS: Between June and August 2018, semi-structured interviews were conducted with 20 MSM and 13 service providers at out-patient clinics (OPCs) and community-based organizations (CBOs) in Hanoi, Vietnam. Interviews explored participants' understandings of and experiences with the signs, causes, and appropriate treatments for mental health concerns; and perceived barriers to MHPSS integration in HIV contexts. Data were coded thematically and analyzed in MAXQDA. RESULTS: Most MSM did not view their mental distress as constituting illness or as warranting clinical attention. Specifically, terms like "mental illness" were often associated with being "crazy" or immoral, while symptoms of distress were interpreted as having to do with everyday difficulties associated with being MSM and/or HIV-positive. Due to mental health stigma, MSM were reluctant to access services while service providers were similarly reluctant to query about needs. Few service providers knew where to refer patients for MHPSS, and none had done so previously. Most service providers reported lacking the human capital, expertise, and funding to address MHPSS needs. CONCLUSIONS: Our findings suggest that aside from mental health stigma, future integration strategies must address competing demands and incentivization structures, limitations in existing mental health infrastructure and funding, misperceptions around MHPSS needs and symptoms, and opportunities to streamline MHPSS with existing CBO activities to strengthen community wellbeing.

Valproate and bone loss: iTRAQ proteomics show that valproate reduces collagens and osteonectin in SMA cells.

Valproate is commonly used as an anticonvulsant and mood stabilizer, but its long-term side-effects can include bone loss. As a histone deacetylase (HDAC) inhibitor, valproate has also been considered for treatment of spinal muscular atrophy (SMA). Using iTRAQ labeling technology, followed by two-dimensional liquid chromatography and mass spectrometry analysis, a quantitative comparison of the proteome of an SMA cell line, with and without valproate treatment, was performed. The most striking change was a reduction in collagens I and VI, while over 1000 other proteins remained unchanged. The collagen I alpha-chain precursor was also reduced by more than 50% suggesting that valproate affects collagen I synthesis. The collagen-binding glycoprotein, osteonectin (SPARC, BM-40) was one of the few other proteins that were significantly reduced by valproate treatment. Collagen I is the main protein component of bone matrix and osteonectin has a major role in bone development, so the results suggest a possible molecular mechanism for bone loss following long-term exposure to valproate. SMA patients may already suffer bone weakness as a result of SMN1 gene deletion, so further bone loss would be undesirable.

The SMN interactome includes Myb-binding protein 1a.

Understanding networks of interacting proteins is a major goal in cell biology. The survival of motor neurons protein (SMN) interacts, directly or indirectly, with a large number of other proteins and reduced levels of SMN cause the inherited disorder spinal muscular atrophy (SMA). Some SMN interactions are stable and stoichiometric, such as those with gemins, while others are expected to be transient and substoichiometric, such as the functional interaction of SMN with coilin in Cajal bodies. This study set out to determine whether novel components of the extensive SMN interactome can be identified by a proteomic approach. SMN complexes were immuno-precipitated from HeLa nuclear extracts, using anti-SMN monoclonal antibody attached to magnetic beads, digested with trypsin, separated by capillary-liquid chromatography and analyzed by MALDI TOF/TOF mass spectrometry. One-hundred and one proteins were detected with a p value of <0.05, SMN, gemins and U snRNPs being the dominant "hits". Sixty-nine of these were rejected after MALDI analysis of two control pull-downs using antibodies against unrelated nuclear proteins. The proteins found only in anti-SMN pulldowns were either known SMN partners, and/or contained dimethylated RG domains involved in direct interaction with the SMN tudor domain, or they were known binding partners of such direct SMN interactors. Myb-binding protein 1a, identified as a novel candidate, is a mainly nucleolar protein of unknown function but it partially colocalized with SMN in Cajal bodies in HeLa cell nucleoplasm and, like SMN, was reduced in cells from an SMA patient.

Learning to predict relapse in invasive ductal carcinomas based on the subcellular localization of junctional proteins.

The complexity of breast cancer biology makes it challenging to analyze large datasets of clinicopathologic and molecular attributes, toward identifying the key prognostic features and producing systems capable of predicting which patients are likely to relapse. We applied machine-learning techniques to analyze a set of well-characterized primary breast cancers, which specified the abundance and localization of various junctional proteins. We hypothesized that disruption of junctional complexes would lead to the cytoplasmic/nuclear redistribution of the protein components and their potential interactions with growth-regulating molecules, which would promote relapse, and that machine-learning techniques could use the subcellular locations of these proteins, together with standard clinicopathological data, to produce an efficient prognostic classifier. We used immunohistochemistry to assess the expression and subcellular distribution of six junctional proteins, in addition to a panel of eight standard clinical features and concentrations of four "growth-regulating" proteins, to produce a database involving 36 features, over 66 primary invasive ductal breast carcinomas. A machine-learning system was applied to this clinicopathologic dataset to produce a decision-tree classifier that could predict whether a novel breast cancer patient would relapse. We show that this decision-tree classifier, which incorporates a combination of only four features (nuclear alpha- and beta-catenin levels, the total level of PTEN and the number of involved axillary lymph nodes), is able to correctly classify patient outcomes essentially 80% of the time. Further, this classifier is significantly better than classifiers based on any subgroup of these 36 features. This study demonstrates that autonomous machine-learning techniques are able to generate simple and efficient decision-tree prognostic classifiers from a wide variety of clinical, pathologic and biomarker data, and unlike other analytic methods, suggest testable biologic relationships among explicitly identified key variables. The decision-tree classifier resulting from these analytic methods is sufficiently simple and should be widely applicable to a spectrum of clinical cancer settings. Further, the subcellular distribution of junctional proteins, which influences growth regulatory pathways involved in locoregional and metastatic relapse of breast cancer, helped to identify which patients would relapse while their total concentration did not. This emphasizes the need to evaluate the subcellular distribution of junctional proteins in assessing their contribution to tumor progression.

The impact of sexual harassment on obesity in female adolescents: An update and perspective to control.

BACKGROUND AND AIMS: Sexual victimization, happened during childhood and beyond, is known to be a substantial contributing factor for obesity development later in life. This work aims to bring about updated information on the relationship between sexual harassment and obesity. METHODS: Based on an intensive scientific literature review in Google Scholar, Pubmed databases, the total of 106 studies (N = 141,199) were assessed including 52 studies on the connection between negative lifetime impacts and obesity, 11 studies on post-traumatic stress disorder (PTSD) symptoms with proposed biological mechanisms related to obesity, 15 studies on the relationship between major depressive disorder (MDD) symptoms and obesity, 11 studies on the body dismorphic disorder (BDD) and 17 studies on the binge eating disorder (BED) were also examined to evaluate the association of obesity and traumatic life experiences. RESULTS: Although 40-70% of all cases related to obesity have been considered to be hereditary, many experts argue that deviations in the environment contribute to excessive food intake and depressed physical activity in numerous Western countries. Several studies have identified that childhood sexual abuse (CSA) may be nearly as common as obesity. However, just a few researchers have taken notice of the possible connection between these two. CONCLUSIONS: By mentioning some possible obesity-related psychological disorders in response to CSA, we present updated information on the relationship between sexual harassment and obesity.

Tamoxifen and ICI 182,780 increase Bcl-2 levels and inhibit growth of breast carcinoma cells by modulating PI3K/AKT, ERK and IGF-1R pathways independent of ERalpha.

We recently showed that estrogen withdrawal from the ERalpha(+), high Bcl-2-expressing breast carcinoma cells (MCF-7B) reduced Bcl-2 protein levels while increasing cell-cell adhesion, and junction formation. Here we compared these cells with the ERalpha(+) and low Bcl-2-expressing MCF-7 cells and with the normal mammary epithelial cell line MCF-10-2A not expressing ERalpha or Bcl-2. All cell lines expressed normal HER2. Antiestrogen (Tamoxifen and ICI 182,780) treatment increased Bcl-2 levels in both MCF-7 and -7B cells and led to the formation of acinar structures. This treatment led to the dissociation of junctions and redistribution of junctional components to the cytoplasm in MCF-10-2A and -7 cells, while in MCF-7B cells junctional proteins redistributed to membranes. Antiestrogen treatment decreased PI3K/Akt activation and increased ERK activation regardless of ERalpha status. IGF-1R was inactivated in the antiestrogen-treated MCF-7 cells while it was activated in MCF-7B cells. Our data show that Tamoxifen and ICI 182,780 can induce growth inhibitory effects via the sustained activation/inactivation of signaling pathways that regulate cell survival, cell death and differentiation in the absence of ERalpha. Furthermore, Bcl-2 overexpression may alter the functional interactions among these pathways in response to antiestrogens, which also may provide a potential explanation for the observation that Bcl-2 overexpressing tumors have a better prognosis.

Nesprin-1-alpha2 associates with kinesin at myotube outer nuclear membranes, but is restricted to neuromuscular junction nuclei in adult muscle.

Nesprins, nuclear envelope spectrin-repeat proteins encoded by the SYNE1 and SYNE2 genes, are involved in localization of nuclei. The short isoform, nesprin-1-alpha2, is required for relocation of the microtubule organizer function from centromeres to the nuclear rim during myogenesis. Using specific antibodies, we now show that both nesprin-1-alpha2 and nesprin-1-giant co-localize with kinesin at the junctions of concatenated nuclei and at the outer poles of nuclear chains in human skeletal myotubes. In adult muscle, nesprin-1-alpha2 was found, together with kinesin, only on nuclei associated with neuromuscular junctions, whereas all adult cardiomyocyte nuclei expressed nesprin-1-alpha2. In a proteomics study, kinesin heavy and light chains were the only significant proteins in myotube extracts pulled down by nesprin-1-alpha2, but not by a mutant lacking the highly-conserved STAR domain (18 amino-acids, including the LEWD motif). The results support a function for nesprin-1-alpha2 in the specific localization of skeletal muscle nuclei mediated by kinesins and suggest that its primary role is at the outer nuclear membrane.

A Rare Colonic Metastasis Case from Hepatocellular Carcinoma.

BACKGROUND: Hepatocellularcarcinoma (HCC) metastasis include intrahepatic and extrahepatic metastasis. Similar to intrahepatic metastasis, extrahepatic metastases are not unusual in cases with HCC. However, colonic metastasis is infrequent. CASE REPORT: We describe a clinical case, he was diagnosed with HCC a year ago, treated with TACE (transarterialchemoembolisation), re-examined with abdominal pain and defecation disorder. The tests such as CT scan, colorectal endoscopy, fine needle aspiration (FNA) revealed secondary metastatic lesion of HCC in sigmoid colon. This is the first gastrointestinal (GI) tract metastatic we have encountered. CONCLUSION: HCC metastases of the colon are rare, especially cases of hematogenous spread. The prognosis of these patients is often very critical. Indications for surgical removal of the lesion may be used if the general situation of patient is acceptable.