[Curcumin alleviates the manganese-induced neurotoxicity by promoting autophagy in rat models of manganism].

OBJECTIVE: To investigate the protective effects of curcumin(CUR) and its mechanism on a rat model of neurotoxicity induced by manganese chloride (MnCl2), which mimics mangnism. METHODS: Sixty male SD rats were randomly divided into 5 groups, with 12 rats in each group. Control group received 0.9% saline solution intraperitoneally (ip) plus double distilled water (dd) H2O intragastrically (ig), MnCl2 group received 15 mg/kg MnCl2(Mn2+ 6.48 mg/kg) intraperitoneally plus dd H2O intragastrically, CUR group received 0.9% saline solution intraperitoneally plus 300 mg/kg CUR intragastrically, MnCl2+ CUR1 group received 15 mg/kg MnCl2 intraperitoneally plus 100 mg/kg curcumin intragastrically, MnCl2+ CUR2 group received 15 mg/kg MnCl2 intraperitoneally plus 300 mg/kg CUR intragastrically, 5 days/week, 4 weeks. Open-field and rotarod tests were used to detect animals' exploratory behavior, anxiety, depression, movement and balance ability. Morris water maze (MWM) experiment was used to detect animals' learning and memory ability. ICP-MS was used to investigate the Mn contents in striata. The rats per group were perfused in situ, their brains striata were removed by brains model and fixed for transmission electron microscope (TEM), histopathological and immunohistochemistry (ICH) analyses. The other 6 rats per group were sacrificed. Their brains striata were removed and protein expression levels of transcription factor EB (TFEB), mammalian target of rapamycin (mTOR), p-mTOR, Beclin, P62, microtubule-associated protein light chain-3 (LC3) were detected by Western blotting. Terminal deoxynucleotidyl transterase-mediated dUTP nick end labeling (TUNEL) staining was used to determine neurocyte apoptosis of rat striatum. RESULTS: After exposure to MnCl2 for four weeks, MnCl2-treated rats showed depressive-like behavior in open-field test, the impairments of movement coordination and balance in rotarod test and the diminishment of spatial learning and memory in MWM (P < 0.05). The striatal TH+ neurocyte significantly decreased, eosinophilic cells, aggregative α-Syn level and TUNEL-positive neurocyte significantly increased in the striatum of MnCl2 group compared with control group (P < 0.05). Chromatin condensation, mitochondria tumefaction and autophagosomes were observed in rat striatal neurocytes of MnCl2 group by TEM. TFEB nuclear translocation and autophagy occurred in the striatum of MnCl2 group. Further, the depressive behavior, movement and balance ability, spatial learning and memory ability of MnCl2+ CUR2 group were significantly improved compared with MnCl2 group (P < 0.05). TH+ neurocyte significantly increased, the eosinophilic cells, aggregative α-Syn level significantly decreased in the striatum of MnCl2+ CUR2 group compared with MnCl2 group. Further, compared with MnCl2 group, chromatin condensation, mitochondria tumefaction was alleviated and autophagosomes increased, TFEB-nuclear translocation, autophagy was enhanced and TUNEL-positive neurocyte reduced significantly in the striatum of MnCl2+ CUR2 group (P < 0.05). CONCLUSION: Curcumin alleviated the MnCl2-induced neurotoxicity and α-Syn aggregation probably by promoting TFEB nuclear translocation and enhancing autophagy.

Sarcopenic Obesity and its Prognostic Impact on Urological Cancers: A Systematic Review.

PURPOSE: Sarcopenia, an age-related loss of muscle mass and function, may predict adverse outcomes for patients with urological cancers. However, the clinical implications and significance of sarcopenic obesity are not well understood. We systematically reviewed data on the prevalence and prognostic impact of sarcopenic obesity for patients with renal cell carcinoma, urothelial carcinoma and prostate cancer undergoing treatment. MATERIALS AND METHODS: We searched EMBASE®, PubMed®/MEDLINE® and Scopus® for relevant original articles and abstracts published between January 2010 and February 2021. Primary outcomes were overall survival (OS), cancer-specific survival (CSS) and progression-free survival. The secondary outcome was the prevalence of sarcopenic obesity. RESULTS: A total of 15 studies comprising 3,866 patients were included. Of the 10 studies that evaluated survival outcomes, the association between sarcopenic obesity and survival was mixed. One of 10 studies showed a significant association of sarcopenic obesity with OS (HR 0.7, 95% CI 0.51-0.98; p=0.04). One additional study showed reported a trend for shorter OS (p=0.05) associated with sarcopenic obesity. Others reported that it is an adverse prognostic factor for CSS (HR 5.0, 95% CI 1.4-16.7; p=0.01). All other studies did not demonstrate that sarcopenic obesity was of prognostic relevance with regard to OS, CSS and progression-free survival. Overall, its mean prevalence was 27% (range 11-63). CONCLUSIONS: There is considerable heterogeneity in methods used to define sarcopenic obesity in the literature, and current data are limited. Future studies are needed to further understand the relationship of obesity and sarcopenia on the clinical trajectory of patients with urological cancer.

Modulation of dendritic cells by endurance training.

A periodized endurance training is able to adapt physical and psychological needs and increase exercise performance. Dendritic cells (DCs) play a key role in regulation of the immune response. In the present study, we trained Sprague-Dawley (SD) rats for five weeks using a progressive endurance protocol with the aim of measuring the effect on myeloid DC differentiation and maturation. Rats were divided into a non-exercise group (NEG) and an exercise group (EG). Bone marrow cells were isolated from these rats after training and cultured in the presence of granulocyte/monocyte-colony stimulatory factor (GM-CSF) and interleukin (IL)-4, and the resultant immature DCs were triggered with lipopolysaccharide to mature. DCs were collected and the main characteristics of DCs were assessed. The recovery rate and the expression of major histocompatibility complex (MHC) class II molecules for DC collected from EG was markedly greater than NEG. The function of DCs from EG to trigger a mixed leukocyte reaction and IL-12 production was higher than NEG. There was no liver and renal toxicity observed in all rats. Changes in food/water consumption and body weight increase between the groups were normal for the conditions. This study demonstrated that periodized endurance training is able to modulate DC development and shift them towards a more mature state.

Effect of a periodized exercise training and active recovery program on antitumor activity and development of dendritic cells.

AIM: Dendritic cells (DCs) are potent antigen-presenting cells that promote antitumor immunity in vivo when pulsed with tumor antigen. No studies have indicated that exercise training affects DC function. The purpose of this study was to investigate the effect of a 5-week periodized exercise training and active recovery program on the development of DCs, and to test their effect on the antitumor immunity of mononuclear cells (MNC) from blood and spleen against human leukemic U937 and murine lymphoma Yac-1 cells, respectively. METHODS: Male Fisher 344 rats were divided into 2 groups: exercise and non-exercise group. The training protocol consisted of running on a motor-driven treadmill 6 days a week for consecutive 5 weeks, during which the running time, treadmill speed, and incline gradient were increased weekly. Active recovery parameters were set at 30% of the intensity of the previous day. RESULTS: DC numbers increased significantly (P<0.05) in the exercise group compared to controls, but there were no significant changes in the expression of surface antigens CD80 and CD86. In exercise group MNC-conditioned medium (CM) prepared with 50 microg/mL phytohemagglutinin (PHA) significantly inhibited proliferation of U937 cells, and splenocyte-CM with PHA at 20 and 40 microg/mL significantly inhibited proliferation of YAC-1 cells greater than control group. CONCLUSIONS: The 5-week periodized exercise training with active recovery promotes the number of DCs and enhances the activity of DCs against tumor cells.

[Primary study of HCV replication in HepG2 cells inoculated by anti-HCV positive and HCVRNA RT-PCR positive serum].

OBJECTIVE: To study HCV replication in HepG2 cell line and to establish a stable HepG2 cell line infected with HCV. METHODS: Continuous inoculation of anti-HVC positive and HCVRNA RT-PCR positive sera was used to infect HepG2 cells. The plus and minus strains of HCVRNA were detected by reverse transcription polymerase chain reaction in the HepG2 cells. Virus particles were observed in postinoculated HepG2 cells by transmission electron microscope. Immunohistochemical staining was used respectively to detect HCV antigen, HCVNS5 and HVC capsid in postinoculated HepG2 cells. RESULTS: HCV RNAs (both plus and minus strains) were found from the first passage to the third passage of postinoculation HepG2 cells, and HCV viruslike particles were detected in the third passage of the infected HepG2 cells, those particles mostly occurred within cytoplasm, their diameters were between 30-60 nm, and gathering silver particles were found in immunogold silver staining of HCV NS5/capsid protein in infected HepG2 cells. Gathering gold particles were found mostly within vesicles in cytoplasm by immuno gold electron microscopy. CONCLUSION: HepG2 cell line infected by HCV is established by continuous inoculation of anti-HCV positive and HCVRNA positive sera. HCV can replicate and produce virus-like particles in HepG2 cells, which may occur in the serial passages of post-infected HepG2 cells.

[Relationship between hot spot mutation in hepatitis B virus basic core promotor and HBeAg status].

OBJECTIVE: This paper was to study the influence of hot spot mutation in hepatitis B virus (HBV) basic core promotor (BCP) (nt1762 and nt1764) on HBeAg status of asymptomatic HBV carriers. METHODS: Mismatched PCR was used to amplify the fragment of HBVBCP and the fragments were analysed by restrict enzyme assay. Ninety cases of HBV infection were tested for hot spot mutations in HBVBCP. RESULTS: Twenty-six (43.3%) of 60 asymptomatic HBV carriers with HBeAg negative were found to have hot spot mutations in HBVBCP, among which 20 cases were accompanied by the mutation of nt 1896 in HBV Pre-C region. Hot-spot mutation in HBVBCP, however, occurred only in 3(10%) of 30 asymptomatic HBV carriers with HBeAg positive. For further investigation the HBVBCP hot spot mutations in asymptomatic HBV carriers without mutation of HBV Pre-C region were studied. Six(31.6%) of 19 asymptomatic HBV carriers with HBeAg negative were found to have hot spot mutation in HBVBCP. Two(7.1%) of 28 asymptomatic HBV carriers with HBeAg positive had hot spot mutations in HBVBCP, and there was a statistically significant difference between two groups. CONCLUSIONS: Hot spot mutations in HBVBCP is common in the HBV carriers with HBeAg negative and usually accompanies with nt1896 mutation of HBV Pre-C region. It is possible that Hot spot mutation in HBVBCP is a new reason of HBeAg negative HBV infection.

Carrier detection in X-linked retinitis pigmentosa.

X-linked retinitis pigmentosa (XLRP) is manifested in affected males in their first decade and results in blindness by the third or fourth decade. Carrier detection is difficult since most carrier females show no or only equivocal signs well into or beyond their reproductive years. The genes, or the mutations causing RP have not been identified but at least two have been localised to the short arm of the X chromosome provisionally named RP2 and RP3. Identifying inheritance of one or other of these genes must be done by linkage in families using close, informative DNA markers. Here we report the localisation of a highly informative polymerase chain reaction (PCR) detectable microsatellite marker DXS538 using a previously studied family with X-linked RP3 in which recombination had occurred in the region of importance. The DXS538 dinucleotide repeat locus was previously localised to Xp21.1-p11.21 to study RP3 in one XLRP family. Using published RFLP data we narrowed the localisation of DXS538 to the region Xp21.1-p11.23. Thus DXS538 is now a convenient diagnostic tool, aiding carrier detection of XLRP in females, as shown in the family presented here.

Exploiting biological materials in forensic science.

One of the important problems in forensic science is the limited availability of biological samples left behind at the scene of the crime. Research in the area of obtaining DNA data from such limited biological samples has resulted in successful court convictions. The ability to carry out DNA fingerprinting from such minute sources relies both on the successful extraction of DNA as well as its subsequent characterisation and analysis. Improved techniques designed to obtain DNA from such samples combined with a small-volume polymerase chain reaction (PCR) and highly informative genetic markers will mean that law enforcement agencies will increasingly be better equipped to deal with violent crime. This review describes some of the sources from which DNA is obtained as well as the techniques used to derive from them valuable genetic information.

A new cathodal Gc variant in Australia.

A new cathodal Gc variant and a known rare variant were found in a study of 307 Australian caucasian blood donors, each with a gene frequency of 0.28%. The frequencies of the other alleles were 0.161 (Gc1F), 0.557 (Gc1S) and 0.279 (Gc2), and were comparable with those of two earlier surveys.

Predisposing locus for Alzheimer's disease on chromosome 21.

Linkage between Alzheimer's disease and markers on the long arm of chromosome 21 was investigated in six families affected by disease of early onset. Linkage was confirmed and the disease locus shown to be centromeric to the locus D21S1/S11 on the long arm of the chromosome. It is argued that the data are consistent with the notion that all patients with Alzheimer's disease of genetic aetiology have a predisposing locus on chromosome 21.

Isoelectric focusing studies of transferrin and haptoglobin subtypes in an Australian white population.

This investigation presents the results of Hp and Tf subtyping of sera from 307 Australian whites by means of isoelectric focusing. Five Hp alleles were detected, these being Hp1F = 0.168, Hp1S = 0.235, Hp2FF = 0.003, Hp2FS = 0.561 and Hp2SS = 0.033. In the Tf system six alleles were found, TfC1 = 0.761, TfC2 = 0.176, TfC3 = 0.054, TfC6 = 0.002, TfB = 0.006 and TfD = 0.002. The usefulness of IEF together with modifications was highlighted for differentiating Tf and Hp subtypes; in particular, the absence of Hp2FF and Hp2SS in some earlier studies could be related to the technique used. The implication of the simultaneous presence of B and D transferrin variants in Caucasian populations is discussed.

Genetic variation in Bougainville and Solomon Islands populations.

This paper reports the findings of genetic variation in eight populations of the Solomon Islands. Blood specimens collected from 345 Aita, 191 Nasioi and 416 Nagovisi of Bougainville, 379 Lau, 453 Baegu and 385 Kwaio of Malaita, and 504 Ontong Java, and 328 Ulawa subjects were tested for A-B-O, M-N-S-s, Rh, Hp, Tf, secretor, and red-cell acid phosphatase systems. Considerable differences were found among the eight populations with respect to all polymorphic systems studied. It was not possible to distinguish Austronesian groups from non-Austronesian groups on the basis of gene frequencies.

Vitamin C and the common cold: using identical twins as controls.

We analysed self-reported cold data for 95 pairs of identical twins who took part in a double-blind trial of vitamin C tablets. One member of each twin pair took vitamin C and the other took a well matched placebo each day for 100 days. Vitamin C had no significant effect except for shortening the average duration of cold episodes by 19%.

A search for association between gene markers and serum cholesterol, triglyceride, urate and blood pressure.

This study was carried out to search for possible association between some polymorphic systems including ABO, MNSs, Rh, Duffy, Kell, Kidd, haptoglobin (Hp) and red cell acid phosphatase (PHs), and the variables serum cholesterol, triglyceride, urate, haemoglobin and blood pressure, in two separate samples of the Australian white population. Allele frequencies of each of the gene marker systems were comparable to those obtained by other workers for Australian whites. There were significant departures from Hardy-Weinberg proportions for red cell acid phosphatase and MNSs systems in one of the samples, and a possible cause for this is discussed. No associations were found between levels of cholesterol, triglyceride, urate and haemoglobin and most of the gene markers in either of the samples. However, a relationship was demonstrated between systolic blood pressure and two polymorphic systems, MNSs and Hp in both populations, and between diastolic blood pressure and red cell acid phosphatase in one of the samples.

Vitamin C and the common cold: a second MZ Cotwin control study.

Self-reported cold data have been analyzed for 95 pairs of identical twins aged 14-64 who took part in a double-blind trial of vitamin C tablets. One member of each twin pair took a tablet containing 1 g vitamin C and the other took a well-matched placebo each day for 100 days. In the total sample there was no effect of vitamin C in preventing colds. However, subdivision of the data showed a significant preventive effect of the placebo in the 51 pairs living together and an equal and opposite preventive effect of the vitamin C in the 44 pairs living apart. The placebo effect in the pairs living together may be attributed to the large proportion who wrongly perceived which treatment they were taking. The reduction of colds in the vitamin C group of the pairs living apart was about 20%. There were significant correlations between cold symptoms reported and the personality trait of neuroticism. No side effects of substantive changes in serum biochemistry could be attributed to the vitamin C dose.

The workshop concept in training of health personnel.

A description is given of the planning, conduct and evaluation of four workshops for health personnel. Components common to all programmes are used to derive a basic model which could be used for educational training training. The results indicate that participants found their workshop experience valuable and relevant to education in the health sciences.

Health status of a group of narcotic addicts in a methadone treatment programme.

This study, which arose out of a concern for the health status of narcotic addicts already in a treatment programme, has demonstrated that there is a severe level of impairment of general health. A summary of important findings is reported. Narcotic addiction leads to secondary medical morbidity and mortality, but health impairment also follows the gross disorder of living which has its roots in childhood, and early adolescent experience. Successful prevention and rehabilitation needs to be based on this knowledge.