Eurycoma longifolia Jack (E. longifolia) is a well-recognized traditional herbal medicine that offers a wide dynamic range of biomedical applications including anti-osteoporotic, anticancer, anti-proliferative, anti-malarial, antimicrobial, antioxidant, aphrodisiac, anti-inflammatory, anxiolytic, anti-diabetic, anti-rheumatism and anti-ulcer properties. This review aims to overview the pharmacokinetic and a pharmacodynamic algorithm of E. longifolia and its bioactive components. Analysis of pharmacokinetic profile revealed that E. longifolia exhibit higher bioavailability, high volume of distribution, slow elimination rate, and does not show inhibitory effects on cytochrome P450 isoenzymes. E. longifolia has been used, alone or in combination with other pharmacological agents, in the form of crude extracts, standard extracts, or decoctions of different plant parts (i.e., herbs, shrubs, stem, leaves, and roots) for the treatment of various ailments in animals and humans. Among various bioactive constituents, eurycomanone has been found to be the most remarkable, super-stable, versatile, and most potent phytochemical (isolated or extracted from root extracts) against various types of animals and human diseases. Based on its well-established pharmacokinetic and pharmacodynamic profiles, we suggested that E. longifolia can be a well-accepted complementary and alternative medicine for the treatment of different types of human ailments.

Elimination of visceral leishmaniasis is a priority programme in Indian subcontinent. The World Health Organization has set a new target to eliminate kala-azar by the year 2020 as previous target elimination year (2015) has passed. The elimination programme has successfully curbed the rate of infection in endemic regions; however, there are still few challenges in its route. The current drug control regime is extremely limited and comprises only two (amphotericin B and miltefosine) drugs, which are also susceptible for parasites resistance. Moreover, these drugs do not produce sterile cure, and cured patients may develop post kala-azar dermal leishmaniasis even after a decade of cure leaving behind a potent source of parasitic reservoirs for further disease transmission. A significant proportion of endemic population remain seropositive but aymptomatic for many years without any clinical symptom that serve as latent parasitic reservoirs. The lack of tools to identify live parasites in asymptomatic infections and there association in disease transmission, parameters of sterile cure along with post kala-azar dermal leishmaniasis progression remain a major threat in its elimination. In this review, we discuss the potential of host immune inhibitory mechanisms to identify immune correlates of protective immunity to understand the mystery of asymptomatic infections, sterile cure and post kala azar dermal leishmaniasis.

Objective: To investigate the fungistatic activity and synergistic effects of natural products and their constituents, including traditional oriental medicines (TOMs). Methods: Fungistatic activities of TOMs prepared by hot-water (115 °C) or ethanol (70%; 40 °C) extraction were determined by their minimum inhibitory concentration. To assess possible synergistic effects, minimum inhibitory concentrations of various combinations were evaluated. Results: By evaluating antifungal susceptibility of Trichophyton rubrum, which is a major causative fungus for several types of dermatophytosis, we confirmed that ethanol extracts were more active than hot-water extracts in 25 of the 36 TOMs, suggesting that the constituents with high hydrophobicity tend to contribute significantly to fungistatic activity. We selected four TOMs with high fungistatic activity, including Aucklandiae radix, Gentianae macrophyllae radix, Scutellariae radix, and Galla rhois, and their synergistic effects were investigated through the combination studies between TOMs or TOM-conventional drug terbinafine. In combinations between four TOMs, partial synergistic effects were observed in Aucklandiae radix–Galla rhois and Gentianae macrophyllae radix–Galla rhois combinations, as supported by the lowest fractional inhibitory concentration index value of 0.66 for both combinations. Furthermore, Galla rhois showed the strongest synergistic effect on growth inhibition of Trichophyton rubrum with a fractional inhibitory concentration index value of 0.50 in combination with terbinafine. Conclusions: Our findings indicate that the combination of TOMs and TOM-terbinafine may be effective on treatment for chronic and recurrent dermatophytosis by improving fungistatic activity and led to decrease systemic toxicity in clinical practice.

Objective: To evaluate the antidiabetic effect of galactomannans extracted from Adenanthera pavonina's L. seeds (GAP) in streptozotocin (STZ) induced diabetic mice. Methods: The preliminary galactomannan yield from Adenanthera pavonina L. plant and extraction products composition were evaluated. Various chemical characterization methods like thin layer chromatography, Fourier transform infrared spectroscopy, ¹H and ¹³C nuclear magnetic resonance, and molecular weight by gel permeation chromatography have been employed to characterize the extracted galactomannan. The mice were divided in four groups: Normal control, diabetic control, GAP (1% and 2%) treated and standard drug treated groups. Diabetic mice received treatment daily for 30 d. Diabetes was induced by STZ at a single dose of 120 mg/kg. Body weight, water and food intake, fasting blood glucose, total cholesterol and triglycerides were measured. Histopathological analysis of pancreas and liver were performed to evaluate STZ-induced tissue injuries. Results: The isolated and extracted galactomannan from Adenanthera pavonina was confirmed by various chemical characterization methods. GAP exhibited a 1.46:1 mannose: galactose ratio, and high molar weight. Both GAP enriched food decreased glycaemia, total cholesterol and triacylglycerol. GAP didn't interfere on food intakes or body weight, although it increased water intake. Furthermore, the relative liver weight indicated toxic galactomannan effects on the histopathological changes of the pancreas in STZ induced diabetes. Conclusions: It is concluded that GAP is a natural product that contains potent galactomannan and is useful in preventing and treating diabetes.

Objective: To investigate the neuroprotective effects of Syzygium aromaticum (S. aromaticum) extract (500 mg/kg) on AlCl₃ (300 mg/kg)-induced mouse model of oxidative stress and neurotoxicity. Methods: An ethanolic extract of S. aromaticum seeds was prepared and the active compounds were identified using nuclear magnetic resonance spectroscopy. BALB/ c mice were divided into five groups (negative control, AlCl₃-treated, self-recovery, AlCl₃ + S. aromaticum, S. aromaticum only; n=10) and treated with AlCl₃ and S. aromaticum extract. Expression of oxidative markers [Superoxide dismutase 1 (SOD1) and peroxiredoxin 6 (Prdx6)] and amyloid precursor protein (APP) in the hippocampus and cortex was evaluated via PCR. Histopathological assessment was performed to investigate the extent of neurodegeneration. Results: It was observed that AlCl₃ exposure increased the expression of APP770 while simultaneously down regulated the expression of APP695. AlCl₃ also induced a significant decrease (P<0.05) and an increase (P<0.05) in the expression level of SOD1 and Prdx6, respectively. A substantial decrease substantial (P<0.05) in the density of Nissl substance was also observed in cortex of the mice treated with AlCl₃. Interestingly, treatment with S. aromaticum extract normalized the alterations in the expression level of SOD1, Prdx6 and APP isoforms and improved the neuronal structural damage. Conclusions: The results showed that S. aromaticum is a promising antioxidant and a neuroprotective agent.

Objective: To represent a new geographical record, Phlebotomus (Adlerius) kabulensis (P. kabulensis), which is suspected to be a potential vector of visceral leishmaniasis. Methods: For the first time, P. kabulensis specimens were collected using the sticky paper traps method in outdoor places in mountainous areas with vegetation coverage of three provinces in Iran. Identification of males was based on ecological, morphological, morphometric and molecular (mtDNA cytochrome b gene sequences) criteria. Generally, males have two ascoids on the 8^th antennal segment and one ascoid on segments 9^th to 15^th, aedeagus with normal obtuse-angled sub-terminal notch and coxite with 27–50 groups of hairs on the distal half of its body. Results: Morphometric measurement revealed that P. kabulensis specimens were the same as compared with seven other morphological characters in three provinces of the country but lengths of the coxite were significantly different. The PCR result of the cytochrome b (Cyt b)-mtDNA fragment shows 550-bp length, with its special nucleotide arrangement. The male and female of P. kabulensis were newly discovered members of the subgenus Adlerius from Iran. Initial DNA analysis indicated how distinct this species is. Conclusions: The results show that the P. kabulensis female will be identified by comparing with other Adlerius female groups regarding its morphometric characters and molecular sequencing.

Objective: To study the effect of RNA interference (RNAi) on WD101 gene and its effect on the expression of WD101 mRNA and protein in Schistosoma japonicum. Methods: Double-stranded RNA (dsRNA) WD101 gene and control gene (lacZ) were generated by in vitro transcription and transfected into mechanically transformed schistosomula. The total RNA and protein were isolated simultaneously using TRIzol reagent. The expression levels of mRNA and the protein were determined by quantitative real-time PCR (qPCR) and Western blotting, respectively. After injected dsRNA-electroporated schistosomula into BALB/c mouse six weeks, the male and female reproductive organs were observed and measured under the confocal laser scanning microscope. Results: After 1, 3 and 5 d of RNAi, WD101 mRNA level was decreased by 15%, 39%, and 58% in experiment group compared to that in control group; meanwhile, WD101 protein level was decreased by 11%, 28%, and 43% in experiment group compared to that in control group. There were significantly more sperms in testicular lobes in experiment group than that in control group, while there were no significant differences in terms of ovary and vitelline glands between two groups. Conclusions: The dsWD101-RNAi can effectively induce suppression of WD101 gene expression at both mRNA and protein levels. WD101 gene might be a reproduction-related gene in Schistosoma japonicum.

Objective: To access the performance of the Tellgenplex human papillomavirus (HPV) DNA test compared to the polymerase chain reaction-reverse dot blot (PCR-RDB) assay for the HPV genotyping. Methods: Sixty cervical swab samples were genotyped by the Tellgenplex HPV DNA test and the PCR-RDB assay. The Tellgenplex HPV DNA test and the PCR-RDB assay can detect 26 and 23 HPV genotypes, respectively. Each sample showed discrepancy was genotyped using sequencing. Results: The percent agreement between the two tests ranged from 83.3% to 100.0% according to different genotype. This showed perfect agreement (>0.81) for high-risk HPV genotypes (35, 39, 45, 53, 56, 59, 66, 68, and 82), substantial agreement (>0.65) for high-risk HPV genotypes (16, 18, 33, 52, and 58) and low-risk HPV genotype 43 between the two assays by the kappa analysis. The positive rates of the two assays for frequent HPV genotypes (16, 35, 39, 45, 52, 53, 58, 59, 66, and 82) were not statistically different, but the PCR-RDB assay showed higher positive rates than the Tellgenplex HPV DNA test for HPV genotypes 81 (P<0.05). As for more than 10 positive results by the Tellgenplex HPV DNA test and/or the PCR-RDB assay, the PCR-RDB assay showed higher relative sensitivity and specificity than the Tellgenplex HPV DNA test for the three HPV genotypes (16, 52, and 81). All HPV genotypes that can be detected by only the Tellgenplex HPV DNA test (HPV genotypes 44 and 55) were confirmed by sequencing. Conclusions: In conclusion, our results demonstrated that the PCR-RDB assay which can detect more multiple HPV genotypes in each specimen shows higher relative sensitivity and specificity than the Tellgenplex HPV DNA test, which makes it a better option for routine clinical use.

Objective: To study the effect of fructose 1,6-diphosphate (FDP) on myocardial ischemia reperfusion injury in rats and its molecular mechanism. Methods: Male SPF SD rats were selected as experimental animals and randomly divided into four groups. Sham group received sham operation, I/R group were made into myocardial ischemia reperfusion injury models, FDP group were made into myocardial ischemia reperfusion injury models and then were given FDP intervention, and FDP+AG490 group were made into myocardial ischemia reperfusion injury models and then were given FDP and JAK2 inhibitor AG490 intervention. Results: CK, CK-MB, cTnI and LDH contents in serum as well as Bax and Caspase-3 protein expression in myocardial tissue of I/R group were significantly higher than those of Sham group whereas Bcl-2, p-JAK2 and p-STAT3 protein expression in myocardial tissues were significantly lower than those of Sham group; CK, CK-MB, cTnI and LDH contents in serum as well as Bax and Caspase-3 protein expression in myocardial tissue of FDP group were significantly lower than those of I/R group whereas Bcl-2, p-JAK2 and p-STAT3 protein expression in myocardial tissue were significantly higher than those of I/R group; CK, CK-MB, cTnI and LDH contents in serum as well as Bax and Caspase-3 protein expression in myocardial tissue of FDP+AG490 group were significantly higher than those of FDP group whereas Bcl-2 protein expression in myocardial tissue was significantly lower than that of FDP group. Conclusion: FDP could reduce the myocardial ischemia reperfusion injury in rats by activating the JAK2/STAT3 pathway.

Objective: To investigate the electrophysiology effects and mechanism of iron overload on the slow response autorhythmic cells in the left ventricular outflow tract of guinea pigs. Methods: Standard microelectrode cell recording techniques were adopted to observe the electrophysiological effects of different concentrations of Fe²⁺ (100 μmol/L, 200 μmol/L) on the left ventricular outflow tract autorhythmic cells. Heart tissues were perfused with FeSO₄ (200 μmol/L) combing with CaC1₂ (4.2 mmol/L), Verapamil, (1 μmol/L), and nickel chloride (200μmol/L) respectively to observe the influences of these contents on electrophysiology of FeSO₄ (200 μmol/L) on the left ventricular outflow tract autorhythmic cells. Results: Fe²⁺ at both 100 μmol/L and 200 μmol/L could change the electrophysiological parameters of the slow response autorhythmic cells of the left ventricular outflow tract in a concentration-dependent manner resulting into decrease in Vmax, APA and MDP, slower RPF and VDD, and prolonged APD₅₀ and APD₉₀ (P all <0.05). Besides, perfusion of increased Ca²⁺ concentration could partially offset the electrophysiological effects of Fe²⁺ (200 μmol/L). The L-type calcium channel (LTCC) blocker Verapamil (1 μmol/L) could block the electrophysiological effects of Fe²⁺ (200 μmol/L). But the T-type calcium channel (TTCC) blocker nickel chloride (NiCl₂, 200 μmol/L) could not block the electrophysiological effects of Fe²⁺ (200 μmol/L). Conclusions: Fe²⁺ can directly change the electrophysiological characteristics of the slow response autorhythmic cells of the left ventricular outflow tract probably through the L-type calcium channel.

Objective: To study the foveal displacement during the closure of idiopathic macular holes (MHs). Methods: Thirty-seven idiopathic MH patients treated by pars plana vitrectomy and internal limiting membrane peeling were studied prospectively. Locations of MH center and foveal pit were measured by optic coherence tomography. Retinal displacement was observed using confocal scanning laser ophthalmoscopy. Results: A total of 40 eyes were included in this study and MHs were closed in 37 eyes (92.5%). The confocal scanning laser ophthalmoscopy showed that all of the retinal capillaries in the superior, inferior, nasal and temporal sides of the MHs moved toward the optic nerve head (ONH). The optic coherence tomography results showed that the mean nasal displacements of foveal pits were (102.9±61.2), (109.6±53.1), and (137.0±52.0) μm at 3, 6 and 12 months, respectively. And the mean vertical displacements were (55.9±49.4), (61.4±57.8) and (67.8±54.3) μm, respectively. Post-operative foveal pits were located in the nasal side of the MH centers. The extension of retina and nasal to the MH were in opposite directions: the nasal hole margin moved toward the MH, but the retina located closer to the ONH moved toward the ONH. The fellow eyes of three patients developed into idiopathic MH during the follow-up period and operations were performed for all of the three patients. Conclusion: Our results showed that center of macula does not move when an idiopathic MH develops, but it moves toward ONH during closure of hole; thus, new fovea is in nasal side of original fovea.

Objective: To assess the effectiveness and safety of lumboperitoneal shunt for treatment of post-traumatic hydrocephalus (PTH). Methods: A retrospective analysis of medical records of patients with lumboperitoneal shunts admitted in Shanghai Tenth People's Hospital from January 2014 to March 2017 was done. Experience with lumboperitoneal shunt placement for PTH was reviewed. The diagnosis of PTH was based on ventricular enlargement with the Evans’ index (EI>0.3) before shunt implantation. Patients were evaluated for improvements in Glasgow Coma Scale (GCS), Glasgow Outcome Scale (GOS), and EI after shunt placement. Results: Totally, the study included 34 PTH patients with the average age of 49.32 years (range: 9-67 years). The average follow-up period was (3.9±3.5) months. Before lumboperitoneal shunt, the GOS score was (4±1), the GCS score was (8.53±3.38), and the EI score was (0.40±0.08). After shunt implantation, the GOS score was (3±1), the GCS score was (10.29±3.15), and the EI score was (0.34±0.13), respectively (P<0.05). Before lumboperitoneal shunt, 24 (70.58%) patients had a GOS score of 4 (vegetative state), and 10 (29.42%) patients had a GOS score of 3 (severe disabled). After lumboperitoneal shunt, 18 (52.94%) patients had improvement in GOS (11 patients improve from GOS 4 to GOS 3, 5 patients from GOS 3 to GOS 2 and 2 patients from GOS 3 to GOS 1), 22 (64.71%) patients achieved improvement in their GCS (14 patients GCS improvements >2 and 8 patients GCS improvement=1), 21 (61.76%) patients had EI improvement (18 patients with EI<0.3). There was no complication in this study. Conclusion: Lumboperitoneal shunt placement is safe and effective for PTH, and serious complications are not observed.

Objective: To investigate the mid-and long-term clinical effects of tricuspid valvuloplasty with the implantation of an artificial plastic ring. Methods: Data of 677 patients who had functional tricuspid regurgitation and left cardiac valve disease and underwent tricuspid valvuloplasty and left cardiac valve surgery were retrospectively. Among these patients, 353 underwent simple suture annuloplasty (group A) while the rest 324 patients underwent artificial plastic ring annuloplasty (group B). The two-year and more-than-two-year clinical and ultrasonocardiograph (UCG) follow-up data of the two groups were obtained and compared. Results: A total of 600 patients (88.6%) completed the long-term follow-up (more than two years). The two-year follow-up showed no significant difference in the incidence of mild tricuspid regurgitation between the two groups (82.2% vs. 92.7%, P=0.37). However, there were significantly more cases that developed into moderate to severe tricuspid regurgitation in group A than in group B (17.8% vs. 7.3%, P=0.031). The long-term follow-up revealed that the recurrence rate of tricuspid regurgitation in group B was significantly lower than that in group A (11.0% vs. 25.0%, P=0.029), and the ratio of cases developing into moderate to severe tricuspid regurgitation in group A was significantly higher than that in group B (28.9% vs. 9.9%, P=0.007). The comparison between the two intra-group time segments showed that the development of tricuspid regurgitation in group A was significantly increased (28.9% vs. 17.8%, P=0.022), but in group B it was relatively stable (9.9% vs. 7.3%, P=0.52). Conclusions: Artificial ring annuloplasty is associated with significantly less tricuspid regurgitation than simple suture annuloplasty.

Objective: To determine the frequency of anti-HCV antibody positivity in patients with non-liver disease complaints, to explore whether anti-HCV positive patients had been properly advised and visited hepatologists for further assessments, and to investigate their clinical characteristics as well as the HCV treatment status. Methods: A hospital based survey of non-liver disease patients with anti-HCV positive and their attending physicians was conducted to determine: 1. were the patients adequately advised of the implication of anti-HCV positive finding; 2. to what extent the patients were aware of potential chronic liver disease associated with HCV infection and whether they sought for further assessments and care of hepatologists. Results: A total of 295 294 non-liver disease patients were tested for anti-HCV antibody, and 2 778 of them were found to be positive (0.94%). However, only 45.10% (1 253/2 778) of the anti-HCV antibody (+) patients were referred to hepatologists and received HCV RNA test. In addition, 34.10% (312/915) and 1.42% (13/915) of them had already advanced to cirrhosis and hepatocellular carcinoma (HCC), respectively. Further analysis showed that the patients who declined antiviral therapy were older, with lower education and lower income, possessed poorer knowledge on the risk of chronic hepatitis C, and had more severe liver diseases. Surprisingly, 65% of the surveyed physicians did not know the genotype-guided treatment duration suggested by the guidelines. Alarmingly, 22% of the surveyed physicians did not know the standard assays for the diagnosis of HCV infection. Conclusions: Our findings highlight the challenge and hidden enormous burden of chronic HCV infection among patients with non-liver disease complaints in China.