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Metabolic syndrome (MetS) has become a major clinical challenge worldwide due to rise of urbanisation, surplus energy intake, increasing obesity and sedentary lifestyle. C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-18 (IL-18) are associated with MetS. We performed a systematic review to investigate the effects of exercise on these markers in MetS patients and therefore to determine the best exercise regime for them. We searched Medline (Pubmed and Ovid), Scopus and CINAHL databases. The searches were standardized by using the same search strategy which included the terms such as ‘metabolic syndrome’, ‘CRP’, ‘IL-6’, ‘IL-18’ and ‘exercise’. Only clinical human studies published from Jan 2007 to May 2018 were included. A total of 11 clinical trials (466 participants) were selected. Majority of the studies were randomized controlled studies (90.9%). All studies showed a decrease in serum levels of the biomarkers. However, not all were statistically significant. The main type of exercise in most of the studies was aerobic. Aerobic-resistance exercise was more effective rather than aerobic alone, but aerobic exercise was the only effective as a sole intervention. Aerobic exercise showed promising role as the main lifestyle intervention in MetS. It is concluded that patients with MetS should have combined aerobic-resistance exercise.

Data on comprehensive population-based surveillance of antimicrobial resistance is lacking. In low- and middle-income countries, the challenges are high due to weak laboratory capacity, poor health systems governance, lack of health information systems, and limited resources. Developing countries struggle with political and social dilemma, and bear a high health and economic burden of communicable diseases. Available data are fragmented and lack representativeness which limits their use to advice health policy makers and orientate the efficient allocation of funding and financial resources on programs to mitigate resistance. Low-quality data means soaring rates of antimicrobial resistance and the inability to track and map the spread of resistance, detect early outbreaks, and set national health policy to tackle resistance. Here, we review the barriers and limitations of conducting effective antimicrobial resistance surveillance, and we highlight multiple incremental approaches that may offer opportunities to strengthen population-based surveillance if tailored to the context of each country.

Vaccine willingness among the mass populace, as well as their proper knowledge and perception regarding vaccines and the vaccination process, may contribute extensively towards attaining their anticipated vaccination rates. The current study endeavored to ascertain the Bangladeshi population’s knowledge, perception, and willingness towards COVID-19 vaccination. Relevant information was collected from 1201 adults aged 18 years or older by employing an online-based survey from 1 to 30 July 2021. Descriptive statistics, the chi-square (χ2) test, and a binary logistic regression analysis were applied in order to compare the extent of knowledge and perception prevalent among different demographic groups and correlate such prevalence with respective vaccine willingness. The participants expressed mean (± standard deviation) knowledge and perception scores of 6.48 ± 1.13 out of 8 and 5.37 ± 1.22 out of 7, respectively. A multivariate analysis confirmed the significant association (p < 0.05) of gender, age, and family income with the knowledge score, whereas age and knowledge level significantly influenced perception. Current living area, family income, and age were considerable contributors to COVID-19 vaccine willingness. Overall vaccine willingness was found to be significantly curtailed by inadequate knowledge (AOR 0.514, CI 95% 0.401–0.658, p < 0.001) and perception (AOR 0.710, CI 95% 0.548–0.920, p = 0.010) among the participants. All of the concerned authorities’ efforts are warranted in order to improve public understanding, perception, and inclination towards vaccination.

Osteoporosis, the most common bone disease, is associated with compromised bone strength and increased risk of fracture. Previous studies have shown that oxidative stress contributes to the progression of osteoporosis. Specifically, for postmenopausal osteoporosis, the reduction in estrogen levels leads to increased oxidative stress in bone remodeling. Tocotrienol, a member of vitamin E that exhibits antioxidant activities, has shown potential as an agent for the treatment of osteoporosis. Most studies on the osteoprotective effects of tocotrienols had used the oral form of tocotrienols, despite their low bioavailability due the lack of transfer proteins and high metabolism in the liver. Several bone studies have utilized tocotrienol combined with a nanocarrier to produce a controlled release of tocotrienol particles into the system. However, the potential of delivering tocotrienol–nanocarrier combination through the intraosseous route has never been explored. In this study, tocotrienol was combined with a nanocarrier, poly lactic-co-glycolic acid (PLGA), and injected intraosseously into the bones of ovariectomized rats to produce targeted and controlled delivery of tocotrienol into the bone microenvironment. This new form of tocotrienol delivery was compared with the conventional oral delivery in terms of their effects on bone parameters. Forty Sprague–Dawley rats were divided into five groups. The first group was sham operated, while other groups were ovariectomized (OVX). Following 2 months, the right tibiae of all the rats were drilled at the metaphysis region to provide access for intraosseous injection. The estrogen group (OVX + ESTO) and tocotrienol group (OVX + TTO) were given daily oral gavages of Premarin (64.5 mg/kg) and annatto-tocotrienol (60 mg/kg), respectively. The locally administered tocotrienol group (OVX + TTL) was given a single intraosseous injection of tocotrienol–PLGA combination. After 8 weeks of treatment, both OVX + TTO and OVX + TTL groups have significantly lower bone markers and higher bone mineral content than the OVX group. In terms of bone microarchitecture, both groups demonstrated significantly higher trabecular separation and connectivity density than the OVX group (p < 0.05). Both groups also showed improvement in bone strength by the significantly higher stress, strain, stiffness, and Young’s modulus parameters. In conclusion, daily oral tocotrienol and one-time intraosseous injection of tocotrienol–PLGA combination were equally effective in offering protection against ovariectomy-induced bone changes.

Background: Recent evolution in terms of technology and availability of the internet has brought several innovations that made work and access to information straightforward. Nonetheless, the danger of pathological internet addiction and its adverse consequences are frightening. Objectives: The primary goal of this research is to determine the level of internet addiction among undergraduate medical students at National Defence University, Malaysia. Methods: A structured questionnaire comprising of section A consisting of student demographic information and section B made up of Dr. Kimberly Young’s 20 items internet addiction test (IAT) in 5-point Likert’s scale. Internet addiction scores were classified based on Young’s scale. Results: The response rate obtained from this study was 89.6%. Out of the 224 respondents, only 4(1.8%) were found to be regular internet users, 98 (43.8%) were established to be mild addicts, 110 (49.1%) were moderate addicts and finally, 12 (5.4%) were severe internet addicts. There was a statistically significant difference in the mean internet addiction score between males and females, with males having higher ratings. Conclusion: The prevalence of internet addiction among undergraduate medical students is high and needs to be controlled. As such, the use of the internet at colleges and universities may need to be regulated. Key words: Internet, Compulsion, Dependence, Apprehension, Medical Student, Smart Phone, Gadgets, Technology, Young’s Internet Addiction Scale.

Panic disorder (PD) being one of the most intensively investigated anxiety disorders is considered a heterogeneous psychiatric disease which has difficulties with early diagnosis. The disorder is recurrent and usually associated with low remission rates and high rates of relapse which may exacerbated social and quality of life, causes unnecessary cost and increased risk for complication and suicide. Current pharmacotherapy for PD are available but these drugs have slow therapeutic onset, several side effects and most patients do not fully respond to these standard pharmacological treatments. Ongoing investigations indicate the need for new and promising agents for the treatment of PD. This article will cover the importance of immediate and proper treatment, the gap in the current management of PD with special emphasis on pharmacotherapy, and evidence regarding the novel anti-panic drugs including the drugs in developments such as metabotropic glutamate (mGlu 2/3) agonist and levetiracetam. Preliminary results suggest the anti-panic properties and the efficacy of duloxetine, reboxetine, mirtazapine, nefazodone, risperidone and inositol as a monotherapy drug. Apart for their effectiveness, the aforementioned compounds were generally well tolerated compared to the standard available pharmacotherapy drugs, indicating their potential therapeutic usefulness for ambivalent and hypervigilance patient. Further strong clinical trials will provide an ample support to these novel compounds as an alternative monotherapy for PD treatment-resistant patient.

Background: Eurycoma longifolia (E. longifolia) has gained remarkable recognition due to its promising efficacy of stimulating bone formation in androgen-deficient osteoporosis. Numerous in vivo studies have explored the effects of E. longifolia on osteoporosis; however, the in vitro cellular mechanism was not discovered yet. Objectives: The present study was aimed to investigate the effect of E. longifolia on the proliferation, differentiation and maturation of osteoclasts and the translational mechanism of inhibition of osteoclastogenesis using RAW 264.7 cells as an in vitro osteoclastic model. Materials and methods: Having assessed cytotoxicity, the cell viability, cell proliferation rate and osteoclastic differentiation capacity of E. longifolia was investigated by evaluating the tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclasts. Taken together, the time-mannered expression of osteoclast-related protein biomarkers such as matrix metallopeptidase-9 (MMP-9), cathepsin-K, TRAP, nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), superoxide (free radicals) generation and superoxide dismutase activity were also measured to comprehend the mechanism of osteoclastogenesis. Results: E. longifolia did not show significant effects on cytotoxicity and cell proliferation of RAW 264.7 cells; however, a significant inhibition of cells differentiation and maturation of osteoclasts was observed. Moreover, a significant down-regulation of RANKL-induced TRAP activity and expression of MMP-9, cathepsin-K, TRAP, NFATc1 and generation of superoxide and enhanced superoxide dismutase activity was observed in E. longifolia treated cell cultures. Conclusion: We anticipated that E. longifolia that enhances bone regeneration on the one hand and suppresses osteoclast’s maturation on the other hand may have great therapeutic value in treating osteoporosis and other bone-erosive diseases such as rheumatoid arthritis and metastasis associated with bone loss. Keywords: Osteoporosis, Eurycoma longifolia, Osteoclasts, Osteoclastogenesis, Bone resorption, Molecular mechanism

COVID-19, transmitted by SARS-CoV-2, is one of the most serious pandemic situations in the history of mankind, and has already infected a huge population across the globe. This horrendously contagious viral outbreak was first identified in China and within a very short time it affected the world's health, transport, economic, and academic sectors. Despite the recent approval of a few anti-COVID-19 vaccines, their unavailability and insufficiency along with the lack of other potential therapeutic options are continuing to worsen the situation, with valuable lives continuing to be lost. In this situation, researchers across the globe are focusing on repurposing prospective drugs and prophylaxis such as favipiravir, remdesivir, chloroquine, hydroxychloroquine, ivermectin, lopinavir-ritonavir, azithromycin, doxycycline, ACEIs/ARBs, rivaroxaban, and protease inhibitors, which were preliminarily based on in vitro and in vivo pharmacological and toxicological study reports followed by clinical applications. Based on available preliminary data derived from limited clinical trials, the US National Institute of Health (NIH) and USFDA also recommended a few drugs to be repurposed i.e., hydroxychloroquine, remdesivir, and favipiravir. However, World Health Organization later recommended against the use of chloroquine, hydroxychloroquine, remdesivir, and lopinavir/ritonavir in the treatment of COVID-19 infections. Combining basic knowledge of viral pathogenesis and pharmacodynamics of drug molecules as well as in silico approaches, many drug candidates have been investigated in clinical trials, some of which have been proven to be partially effective against COVID-19, and many of the other drugs are currently under extensive screening. The repurposing of prospective drug candidates from different stages of evaluation can be a handy wellspring in COVID-19 management and treatment along with approved anti-COVID-19 vaccines. This review article combined the information from completed clinical trials, case series, cohort studies, meta-analyses, and retrospective studies to focus on the current status of repurposing drugs in 2021.

Antimicrobial resistance remains a significant public health issue, and to a greater extent, caused by the misuse of antimicrobials. Monitoring and benchmarking antimicrobial use is critical for the antimicrobial stewardship team to enhance prudent use of antimicrobial and curb antimicrobial resistance in healthcare settings. Employing a comprehensive and established tool, this study investigated the trends and compliance of antimicrobial prescribing in a tertiary care teaching hospital in Malaysia to identify potential target areas for quality improvement. A point prevalence survey method following the National Antimicrobial Prescribing Survey (NAPS) was used to collect detailed data on antimicrobial prescribing and assessed a set of quality indicators associated with antimicrobial use. The paper-based survey was conducted across 37 adult wards, which included all adult in-patients on the day of the survey to form the study population. Of 478 patients surveyed, 234 (49%) patients received at least one antimicrobial agent, with 357 antimicrobial prescriptions. The highest prevalence of antimicrobial use was within the ICU (80%). Agents used were mainly amoxicillin/β-lactamase inhibitor (14.8%), piperacillin/β-lactamase inhibitor (10.6%) and third-generation cephalosporin (ceftriaxone, 9.5%). Intravenous administration was ordered in 62.7% of prescriptions. Many antimicrobials were prescribed empirically (65.5%) and commonly prescribed for pneumonia (19.6%). The indications for antimicrobials were documented in the patients’ notes for 80% of the prescriptions, however, the rate of review/stop date recorded must be improved (33.3%). One-half of surgical antimicrobial prophylaxis was administered for more than 24 h. From 280 assessable prescriptions, 141 (50.4%) were compliant with guidelines. Treating specialties, administration route, class of antimicrobial, and the number of prescriptions per patient were contributing factors associated with compliance. On multivariate analysis, administering non-oral routes of antimicrobial administration, and single antimicrobial prescription prescribed per patient was independently associated with non-compliance. NAPS can produce robust baseline information and identifying targets for improvement in antimicrobial prescribing in reference to current AMS initiatives within the tertiary care teaching hospital. The findings underscore the necessity to expand the AMS efforts towards reinforcing compliance, documentation, improving surgical prophylaxis prescribing practices, and updating local antibiotic guidelines.

Edible bird’s nest (BN) is a Chinese traditional medicine with innumerable health benefits, including anti-viral, anti-inflammatory, neuroprotective, and immunomodulatory effects. A small number of studies have reported the anti-viral effects of EBN against influenza infections using in vitro and in vivo models, highlighting the importance of sialic acid and thymol derivatives in their therapeutic effects. At present, studies have reported that EBN suppresses the replicated virus from exiting the host cells, reduces the viral replication, endosomal trafficking of the virus, intracellular viral autophagy process, secretion of pro-inflammatory cytokines, reorient the actin cytoskeleton of the infected cells, and increase the lysosomal degradation of viral materials. In other models of disease, EBN attenuates oxidative stress-induced cellular apoptosis, enhances proliferation and activation of B-cells and their antibody secretion. Given the sum of its therapeutic actions, EBN appears to be a candidate that is worth further exploring for its protective effects against diseases transmitted through air droplets. At present, anti-viral drugs are employed as the first-line defense against respiratory viral infections, unless vaccines are available for the specific pathogens. In patients with severe symptoms due to exacerbated cytokine secretion, anti-inflammatory agents are applied. Treatment efficacy varies across the patients, and in times of a pandemic like COVID-19, many of the drugs are still at the experimental stage. In this review, we present a comprehensive overview of anti-viral and anti-inflammatory effects of EBN, chemical constituents from various EBN preparation techniques, and drugs currently used to treat influenza and novel coronavirus infections. We also aim to review the pathogenesis of influenza A and coronavirus, and the potential of EBN in their clinical application. We also describe the current literature in human consumption of EBN, known allergenic or contaminant presence, and the focus of future direction on how these can be addressed to further improve EBN for potential clinical application.

SARS-CoV-2 is the latest worldwide pandemic declared by the World Health Organization and there is no established anti-COVID-19 drug to combat this notorious situation except some recently approved vaccines. By affecting the global public health sector, this viral infection has created a disastrous situation associated with high morbidity and mortality rates along with remarkable cases of hospitalization because of its tendency to be high infective. These challenges forced researchers and leading pharmaceutical companies to find and develop cures for this novel strain of coronavirus. Besides, plants have a proven history of being notable wellsprings of potential drugs, including antiviral, antibacterial, and anticancer therapies. As a continuation of this approach, plant-based preparations and bioactive metabolites along with a notable number of traditional medicines, bioactive phytochemicals, traditional Chinese medicines, nutraceuticals, Ayurvedic preparations, and other plant-based products are being explored as possible therapeutics against COVID-19. Moreover, the unavailability of effective medicines against COVID-19 has driven researchers and members of the pharmaceutical, herbal, and related industries to conduct extensive investigations of plant-based products, especially those that have already shown antiviral properties. Even the recent invention of several vaccines has not eliminated doubts about safety and efficacy. As a consequence, many limited, unregulated clinical trials involving conventional mono- and poly-herbal therapies are being conducted in various areas of the world. Of the many clinical trials to establish such agents as credentialed sources of anti-COVID-19 medications, only a few have reached the landmark of completion. In this review, we have highlighted and focused on plant-based anti-COVID-19 clinical trials found in several scientific and authenticated databases. The aim is to allow researchers and innovators to identify promising and prospective anti-COVID-19 agents in clinical trials (either completed or recruiting) to establish them as novel therapies to address this unwanted pandemic.

Dengue, a very widespread mosquito-borne infectious disease caused by Aedes aegypti virus, has been occurring during the monsoons every year. The prevalence and incidence of dengue fever and death due to its complications have been increased drastically in these recent years in Bangladesh, Philippines, Thailand, Brazil, and India. Recently, dengue had spread in an epidemic form in Bangladesh, Thailand, and Philippines. Although the infection affected a large number of people around the world, there is no established specific and effective treatment by synthetic medicines. In this subcontinent, Malaysia could effectively control its incidences and death of patients using alternative medication treatment mainly prepared from Carica papaya L. leaves along with proper care and hospitalization. Papaya leaves, their juice or extract, as well as their different forms of preparation have long been used traditionally for treating dengue fever and its complications to save patients’ lives. Although it is recommended by traditional healers, and the general public use Papaya leaves juice or their other preparations in dengue fever, this treatment option is strictly denied by the physicians offering treatment in hospitals in Bangladesh as they do not believe in the effectiveness of papaya leaves, thus suggesting to patients that they should not use them. In Bangladesh, 1,01,354 dengue patients have been hospitalized, with 179 deaths in the year 2019 according to information from the Institute of Epidemiology, Disease Control, and Research as well as the Directorate General of Health Services of Bangladesh. Most of the patients died because of the falling down of platelets to dangerous levels and hemorrhage or serious bleeding. Therefore, this paper aims to critically review the scientific basis and effectiveness of Carica papaya L. leaves in treating dengue fever based on preclinical and clinical reports. Thrombocytopenia is one of the major conditions that is typical in cases of dengue infection. Besides, the infection and impairment of immunity are concerned with dengue patients. This review summarizes all the scientific reports on Carica papaya L. for its ability on three aspects of dengue: antiviral activities, prevention of thrombocytopenia and improvement of immunity during dengue fever.

Background Colocasia gigantea, locally named as kochu is well-known due to its various healing power. This research is to investigate the antidiarrheal, antimicrobial and antioxidant possibilities of the methanol soluble extract of Colocasia gigantea. Methods The antidiarrheal investigation was performed by using in vivo castor oil-induced diarrheal method whereas in vitro antimicrobial and antioxidant investigation have been implemented by disc diffusion and DPPH scavenging method respectively. Moreover, in silico studies were followed by molecular docking analysis of several secondary metabolites that were appraised with Schrödinger-Maestro v11.1 and Biovia Discovery Studio. Results The induction of plant extract (200 and 400 mg/kg, b.w, p.o) has minimized the castor oil mediated diarrhea by 16.96% (p p C. gigantea showed mild sensitivity against almost all the tested strains but it shows high consistency of phenolic content and yielded 67.68 μg/mL of IC50 value in the DPPH test. In the PASS prediction, selected isolated compounds have demonstrated significant antidiarrheal and antimicrobial activity following the Lipinski drug rules which have ascertained efficacy with the compounds in molecular docking study. Conclusion The results of this scientific research reflects that the methanol soluble extract of C. gigantea is safe and may provide possibilities of alleviation of diarrhea along with being a potential wellspring of antioxidant and antimicrobial agents which can be considered as an alternate source for exploration of new medicinal products in near future.

The article's abstract is not available.

Autism spectrum disorder (ASD) is a neurodevelopmental condition of the central nervous system (CNS) that presents with severe communication problems, impairment of social interactions, and stereotypic behaviours. Emerging studies indicate possible associations between viral infections and neurodegenerative and neurobehavioural conditions including autism. Viral infection during critical periods of early in utero neurodevelopment may lead to increased risk of autism in the offspring. This review is aimed at highlighting the association between viral infections, including viruses similar to COVID-19, and the aetiology of autism. A literature search was conducted using Pubmed, Ovid/Medline, and Google Scholar database. Relevant search terms included “rubella and autism”, “cytomegalovirus and autism”, “influenza virus and autism”, “Zika virus and autism”, “COVID-19 and autism”. Based on the search terms, a total of 141 articles were obtained and studies on infants or children with congenital or perinatal viral infection and autistic behaviour were evaluated. The possible mechanisms by which viral infections could lead to autism include direct teratogenic effects and indirect effects of inflammation or maternal immune activation on the developing brain. Brain imaging studies have shown that the ensuing immune response from these viral infections could lead to disruption of the development of brain regions and structures. Hence, long-term follow up is necessary for infants whose mothers report an inflammatory event due to viral infection at any time during pregnancy to monitor for signs of autism. Research into the role of viral infection in the development of ASD may be one avenue of improving ASD outcomes in the future. Early screening and diagnosis to detect, and maybe even prevent ASD are essential to reduce the burden of this condition.

Oxidative stress and inflammation are two common risk factors of various life-threatening disease pathogenesis. In recent years, medicinal plants that possess antioxidant and anti-inflammatory activities were extensively studied for their potential role in treating and preventing diseases. Spilanthes acmella (S. acmella), which has been traditionally used to treat toothache in Malaysia, contains various active metabolites responsible for its anti-inflammatory, antiseptic, and anesthetic bioactivities. These bioactivities were attributed to bioactive compounds, such as phenolic, flavonoids, and alkamides. The review focused on the summarization of in vitro and in vivo experimental reports on the antioxidant and anti-inflammatory actions of S. acmella, as well as how they contributed to potential health benefits in lowering the risk of diseases that were related to oxidative stress. The molecular mechanism of S. acmella in reducing oxidative stress and inflammatory targets, such as inducible nitric oxide synthase (iNOS), transcription factors of the nuclear factor-κB family (NF-κB), cyclooxygenase-2 (COX-2), and mitogen-activated protein kinase (MAPK) signaling pathways were discussed. Besides, the antioxidant potential of S. acmella was measured by total phenolic content (TPC), total flavonid content (TFC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and superoxide anion radical scavenging (SOD) and thiobarbituric acid reactive substance (TBARS) assays. This review revealed that S. acmella might have a potential role as a reservoir of bioactive agents contributing to the observed antioxidant, anti-inflammatory, and health beneficial effects.

Marantodes pumilum (MP) is a great source of herbal medicine used traditionally by both men and women for various purposes. MP may have potential wound-healing effects due to its diverse biological properties. An extensive study was conducted in a normal male rat model for determining the effects of MP var. pumila (MPvp) and var. alata (MPva) on the wound healing process. Here, 126 male Sprague-Dawley rats were divided randomly into seven groups as follows: sham-operated (SH), vehicle dressing (VD), flavine dressing (FD), MPvp leaves (PL), MPvp roots (PR), MPva leaves (AL), and MPva roots (AR). The parameters studied were the percentage of wound contraction, histomorphology study by hematoxylin and eosin (H&amp, E), Masson&ndash, Goldner trichrome (MGT), and immunohistochemistry (IHC) staining. In addition, the levels of enzymatic antioxidants and malondialdehyde were also measured in the wound tissue homogenates. Wounds treated with extracts (PL, PR, AL, and AR) showed significantly faster healing (p &lt, 0.05) compared to untreated and control groups (SH, VD, and FD). Histological analysis among MP-treated groups revealed better re-epithelialization, higher collagen deposition, enhanced fibronectin content and fibroblast cells, and higher fiber transformation from collagen-III to collagen-I, accompanied with a significant surge in enzymatic antioxidant activities and a decline in lipid peroxidation. MP has antioxidant effects that may enhance wound healing in the rat model.

Clinical characteristics are essential for the correct diagnosis of diseases. The current review aimed to summarize the global clinical characteristics of the COVID-19 patients systematically and identify their diagnostic challenges to help the medical practitioners properly diagnose and for better management of COVID-19 patients. We conducted a systematic search in PubMed, Web of Science, Scopus, Science Direct, and Google Scholar databases for original articles containing clinical information of COVID-19 published up to 7th May 2020. Two researchers independently searched the databases to extract eligible articles. A total of 34 studies from 8 different countries with 10889 case-patients were included for clinical characteristics. The most common clinical symptoms were cough 59.6, fever 46.9, fatigue 27.8, and dyspnea 20.23%. The prominent laboratory findings were lymphocytopenia 55.9, elevated levels of CRP 61.9, aspartate aminotransferase 53.3, LDH 40.8, ESR 72.99, serum ferritin 63, IL-6 52, and prothrombin time 35.47%, and decreased levels of platelets 17.26, eosinophils 59.0, hemoglobin 29, and albumin 38.4%. CT scan of the chest showed an abnormality in 93.50% cases with bilateral lungs 71.1%, ground-glass opacity 48%, lesion in lungs 78.3%, and enlargement of lymph node 50.7%. Common comorbidities were hypertension, diabetes, obesity, and cardiovascular diseases. The estimated median incubation period was 5.36 days, and the overall case fatality rate was 16.9% (Global case fatality outside China was 22.24%: USA 21.24%, Italy 25.61%, and others 0%; whereas the case fatality inside the Hubei Province of China was found to be 11.71%). Global features on the clinical characteristics of COVID-19 obtained from laboratory tests and CT scan results will provide useful information to the physicians to diagnose the disease and for better management of the patients as well as to address the diagnostic challenges to control the infection.

Cardiovascular diseases (CVD) have been recognized as the leading cause of mortality worldwide, accounting for 31% of global mortality. Among the risk factors of CVD, hyperlipidemia has been established as the most potent risk factor. Statins, a class of drug that reduces lower-density lipoprotein cholesterol (LDL-C), are the preferred medical treatment. However, due to the development of statin-associated muscle symptoms, statins are associated with patients’ discontinuation and nonadherence. Other statin-induced side effects, such as hepatotoxicity and gastrointestinal upset, all contribute to patients choosing alternative medicines. Squalene (SQ), an unsaturated hydrocarbon naturally synthesized in plants and animals, could become the alternative treatment or supplementary agent for cardiovascular health. SQ has been shown to exert cardioprotective effect via its antioxidant activity. Oxidative stress and inflammatory responses are closely related to each other, which proposes an interdependence relation between antioxidant and anti-inflammatory. Therefore, this review explores the interdependence between the antioxidant and anti-inflammatory effects of SQ implicated on cardiovascular health.

Neurodegenerative diseases (ND) can be characterized by degradation and subsequent loss of neurons. ND has been identified as the leading cause of disability-adjusted life years (DALYs) worldwide and is associated with various risk factors such as ageing, certain genetic polymorphisms, inflammation, immune and metabolic conditions that may induce elevated reactive oxygen species (ROS) release and subsequent oxidative stress. Presently, no specific cure or prevention is available for ND patients; the symptoms can be only alleviated via drug treatment or surgery. The existing pharmacological treatments are only available for partial treatment of the symptoms. A natural product known as oil palm phenolics (OPP), which is high in antioxidant, could become a potential supplementary antioxidant for neurodegenerative health. OPP is a water-soluble extract from palm fruit that demonstrated medicinal properties including anti-tumor, anti-diabetic and neuroprotective effects. In this review, OPP was proposed for its neuroprotective effects via several mechanisms including antioxidant and anti-inflammatory properties. Besides, OPP has been found to modulate the genes involved in neurotrophic activity. The evidence and proposed mechanism of OPP on the neuroprotective health may provide a comprehensive natural medicine approach to alleviate the symptoms of neurodegenerative diseases.

The repeatability of most questionnaires utilized in previous studies related to the consumption of dietary supplements (DS) among youth has not been well documented. Thus, a simple and easy-to-administer questionnaire to capture the habitual use of DS in the past one year known as the dietary supplement questionnaire (DiSQ) was developed and supported with external reliability evaluation. Analyses were done based on a convenience sample of 46 secondary school students. To elicit information regarding the intake of DS, the questionnaire was partitioned into two domains. The first domain was used to identify vitamin/mineral (VM) supplements, while the second domain was utilized to identify non-vitamin/non-mineral (NVNM) supplements. Cohen&rsquo, s kappa coefficient (k) was used to evaluate the test&ndash, retest reliability of the questionnaire. Questionnaire administration to the respondents was done twice whereby a retest was given two weeks after the first test. Between test and retest, the reliability of individual items ranged from moderate to almost perfect for the VM (k = 0.53&ndash, 1.00) and NVNM (k = 0.63&ndash, 1.00) domains. None of the items had &ldquo, fair&rdquo, or &rdquo, poor&rdquo, agreement. Various correlation coefficients can be obtained for the DiSQ but are generally reliable over time for assessing information on the consumption of supplements among the adolescent population.

Alcohol use disorder (AUD) has been associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Prolonged excessive alcohol intake contributes to increased production of reactive oxygen species that triggers neuroimmune response and cellular apoptosis and necrosis via lipid peroxidation, mitochondrial, protein or DNA damage. Long term binge alcohol consumption also upregulates glutamate receptors, glucocorticoids and reduces reuptake of glutamate in the central nervous system, resulting in glutamate excitotoxicity, and eventually mitochondrial injury and cell death. In this review, we delineate the following principles in alcohol-induced neurodegeneration: (1) alcohol-induced oxidative stress, (2) neuroimmune response toward increased oxidants and lipopolysaccharide, (3) glutamate excitotoxicity and cell injury, and (4) interplay between oxidative stress, neuroimmune response and excitotoxicity leading to neurodegeneration and (5) potential chronic alcohol intake-induced development of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease.

The article's abstract is no available.

Cardiovascular disease (CVD) is globally known as the number one cause of death with hyperlipidemia as a strong risk factor for CVD. The initiation of drug treatment will be recommended if lifestyle modification fails. However, medicines currently used for improving cholesterol and low-density lipoprotein cholesterols (LDL-C) levels have been associated with various side effects. Thus, alternative treatment with fewer or no side effects needs to be explored. A potential agent, oil palm phenolics (OPP) recovered from the aqueous waste of oil palm milling process contains numerous water-soluble phenolic compounds. It has been postulated that OPP has shown cardioprotective effects via several mechanisms such as cholesterol biosynthesis pathway, antioxidant and anti-inflammatory properties. This review aims to summarize the current evidence explicating the actions of OPP in cardiovascular health and the mechanisms that maybe involved for the cardioprotective effects.

Background and purpose Physical function assessment can be performed to assess functional mobility among older adults, especially after a traumatic incident such as lower body fracture (LBF). The objective of this study was to evaluate physical function of older patients with LBF after 3 months of discharge from the hospital. Patients and methods A total of 89 patients were followed up at the discharge phase. Four independent variables were tested: age, sex, type of fracture, and use of a walking aid before fracture. Mobility and strength were assessed with the Timed Up and Go (TUG) test and hand-grip strength (HGS) test, respectively. Results The majority of the patients were ≥65 years old (64%), female (61.8%), of Chinese ethnicity (50.6%), and had a hip fracture (51.7%). The mean time for TUG test was 26.11 seconds, while mean HGS was 19.02 kg. We found significant differences in TUG test scores with respect to all independent variables tested: age (P=0.026), sex (P=0.011), fracture type (P

Sexual dysfunction has been extensively studied in methadone maintenance treatment (MMT) patients. However, little data is available regarding sexual inactivity in the MMT patient population. The objectives of this study were to determine the prevalence and putative risk factors for sexual inactivity in the MMT patient population. This cross-sectional study involved 25&ndash, 71 year old MMT patients recruited from six methadone clinics. Two hundred and seventy-one patients were interviewed for demographic characteristics, comorbidities, concurrent medications used, and sexual activity. The prevalence of sexual inactivity in the MMT population was found to be 47.6%. Increasing age (p &lt, 0.01) and being single/divorced (p &lt, 0.01) were significantly associated with sexual inactivity. In subgroup analysis, increasing age was significantly associated with sexual inactivity in both single/divorced (p &lt, 0.05) and married (p &lt, 0.05) subgroups, while unemployment (p &lt, 0.05) was only significantly associated with sexual inactivity in the earlier subgroup. Our results suggest that sexual inactivity is common in the MMT patient population. The putative risk factors are related to biological and sociocultural factors. Having specific comorbidities or being on certain medications were not correlated with sexual inactivity in the MMT population. Routine assessment of sexual problems is essential, and proper management should be performed for MMT patients.

Background:Phytoestrogens have recently been claimed to positively influence menopausal discomforts, including hot flashes. However, little is known about the influence of phytoestrogens on core body temperature during oestrogen fluctuation at menopause.Objective:Previously published findings showed that phytoestrogens could relieve menopausal complaints, thus, the present review was aimed at assessing the effects of phytoestrogens on thermoregulatory mechanism during menopausal transition.Results:The molecular mechanisms underlying hot flashes are complex. Oestrogen fluctuations cause hypothalamic thermoregulatory centre dysfunction, which leads to hot flashes during menopause. The phytoestrogens of interest, in relation to human health, include isoflavones, lignans, coumestans, and stilbenes, which are widely distributed in nature. The phytoestrogens are capable of reducing hot flashes via their oestrogen-like hormone actions. The potential effects of phytoestrogens on hot flashes and their molecular mechanisms of action on thermoregulatory centre are discussed in this review.Conclusion:The effects of phytoestrogens on these mechanisms may help explain their beneficial effects in alleviating hot flashes and other menopausal discomforts.

Ficus carica, a native plant to the Middle East and Western Asia, is of high value in folk medicine. The therapeutic potential of Ficus carica has led to the extensive studies in recent years, focusing on evaluating and validating its pharmacological effect. The present systematic review summarizes the effectiveness of Ficus carica on promoting bone health focusing on osteoporosis and rheumatoid arthritis via mineral contents and RANKL pathway. The search was done with Medline via Ebscohost, Scopus and Google Scholar databases to obtain relevant articles published between 1946 and December 2016. The main inclusion criteria were research articles published in English that reported effect of Ficus carica on bone health. The literature search returned 716 potentially relevant articles, whereby 5 met the inclusion criteria. This systematic review concludes Ficus carica plays an important role in the promotion of bone health and can be a potential pharmaceutical product in the future.

Background Eurycoma longifolia (E. longifolia) has gained widespread recognition due to its versatile pharmacological activities including aphrodisiac, anticancer, antimicrobial, antioxidant, anti-inflammatory, anxiolytic, anti-diabetic, ergogenic, insecticidal, anti-rheumatism, bone protection, and anti-ulcer effects. Objective This review was aimed to critically overview the literature and summarizes the antibacterial, antiprotozoal, and antifungal trends of E. longifolia and its medicinally active components. Results Besides its well-documented safety, efficacy, and tolerability, a plethora of in vitro, in vivo, and human clinical studies has evidenced the antimicrobial efficacy of E. longifolia and its bioactive constituents. Phytochemical screening of various types of extracts (methanolic, ethyl acetate, and nbutanolic) from different parts (roots, stem, and leaves) of E. longifolia displayed a dose-dependent antibacterial, antiprotozoal, and antifungal responses. Comparative analysis revealed that the root extract of E. longifolia exhibited the highest antimicrobial efficacy compared to other parts of the plant. Bioactivity-guided fractionation identified that among all of the medicinal compounds isolated/ extracted from different parts of E. longifolia, eurycomanone displayed the strongest antibacterial, antiprotozoal and antifungal activities. Conclusion Based on the critical analysis of the literature, we identified that E. longifolia exhibits promising antibacterial, antiprotozoal, and antifungal efficacies against various pathogenic microbes and thus can be considered as a potential complementary and alternative antimicrobial therapy.

Background Eurycoma longifolia is a well-documented herbal medicine that has gained widespread recognition due to its versatile pharmacological activities including anticancer, antimalarial, antimicrobial, antioxidant, aphrodisiac, anti-inflammatory, anxiolytic, anti-diabetic, antirheumatism and anti-ulcer. Plethora of in vitro and in vivo studies evidenced their excellent antiproliferative and anticancer efficacy against various types of human cancers. Objective This review was aimed to critically analyze the therapeutic viability and anticancer efficacy of Eurycoma longifolia in the treatment of cancer and also to propose its molecular and translational mechanism of cytotoxicity against cancerous cells. Results Among a range of medicinally active compounds isolated from various parts (roots, stem, bark and leaves) of Eurycoma longifolia, 16 compounds have shown promising anti-proliferative and anticancer efficacies. Eurycomanone, one of the most active medicinal compounds of Eurycoma longifolia, displayed a strong dose-dependent anticancer efficacy against lung carcinoma (A-549 cells) and breast cancer (MCF-7 cells); however, showed moderate efficacy against gastric (MGC-803 cells) and intestinal carcinomas (HT-29 cells). The prime mode of cytotoxicity of Eurycoma longifolia and its medicinal compounds is the induction of apoptosis (programmed cell death) via the up-regulation of the expression of p53 (tumor suppressor protein) and pro-apoptotic protein (Bax) and downregulation of the expression of anti-apoptotic protein (Bcl-2). A remarkable alleviation in the mRNA expression of various cancer-associated biomarkers including heterogeneous nuclear ribonucleoprotein (hnRNP), prohibitin (PHB), annexin-1 (ANX1) and endoplasmic reticulum protein-28 (ERp28) has also been evidenced. Conclusion Eurycoma longifolia and its medicinal constituents exhibit promising anticancer efficacy and thus can be considered as potential complementary therapy for the treatment of various types of human cancers.

Marantodes pumilumis a herbaceous plant that has widely recognized for its medicinal use. The plant used widely has led to many studies on its phytochemical identification, pharmacological and toxicological activities. Phytoconstituents found in theMarantodes pumilumextracts showed high antioxidant and anti-inflammatory properties which are essential for many pharmacological effects. The aim of the systematic review is to provide the information of antioxidant and anti-inflammatory properties found inMarantodes pumilum. A critical literature search from three electronic databases such as SCOPUS, EBSCOhost and Ovid Medline was conducted for related studies published from the years 1946 to November 2017. The research studies published in English and related with the antioxidant and anti-inflammatory effects ofMarantodes pumilumwere the main inclusion criteria in this review. A total 512 relevant articles was identified, whereby 21 articles met the inclusion criteria. Twelve chemical assay studies, five animal studies, twoin vitrocell culture study, one combinedin vivoanimal and chemical study and one combined chemical assay andin vitrocell culture study included in this review. All of the studies reported moderate to noticeable positive effects ofMarantodes pumilumagainst oxidation and inflammation. This systematic review highlights the antioxidant and anti-inflammatory effects and their relation with phytoconstituents ofMarantodes pumilumextracts.

Neurodegenerative disease is an incurable disease which involves the degeneration or death of the nerve cells. Alzheimer’s Disease (AD) is a neurodegenerative disease discovered in 1906 by Alois Alzheimer, a German clinical psychiatrist and neuroanatomist. The main pathological hallmarks of this disease are the formation of extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangle (NFT). The accumulation of the amyloid protein aggregates in the brain of AD patients leads to oxidative stress and inflammation. Other postulated reasons for the development of this disease are cholinergic depletion and excessive glutamatergic neurotransmission. The current drugs approved and marketed for the treatment of AD are cholinesterase inhibitors (ChEIs) and N-methyl-D-aspartate (NMDA) receptor antagonists. The function of ChEIs is to avoid cholinergic depletion; whereas the function of NMDA receptor antagonist is to block excessive glutamatergic neurotransmission. Unfortunately, the current drugs prescribed for AD show only modest improvement in terms of symptomatic relief and delay the progression of the disease. This review will discuss about several polyphenolic compounds as potential natural treatment options for AD. Three compounds are highlighted in this review — Curcumin (Cur), Resveratrol (Rsv) and Epigallocatechin-3-gallate (EGCG). These compounds have huge potential for AD treatment, especially due to their low frequency of adverse events. However, the current conventional pharmaceutical drugs remain as the mainstay of treatment for AD.

Plant phenolics are being increasingly consumed globally with limited scientific and clinical evidence pertaining to safety and efficacy. The oil palm fruit contains a cocktail of phenolics, and palm oil production results in high volumes of aqueous by-products enriched in phenolics and bioactives. Several lines of evidence from in vitro and in vivo animal studies confirmed that the aqueous extract enriched in phenolics and other bioactives collectively known as oil palm phenolics (OPP) is safe and has potent bioactivity. A phase one clinical trial was conducted to evaluate the safety and effects of OPP in healthy volunteers. In this single-blind trial, 25 healthy human volunteers were supplemented with 450 mg gallic acid equivalent (GAE)/day of OPP or control treatments for a 60-day period. Fasting blood and urine samples were collected at days 1, 30 and 60. Medical examination was performed during these trial interventions. All clinical biochemistry profiles observed throughout the control and OPP treatment period were in the normal range with no major adverse effect (AE) or serious adverse effect (SAE) observed. Additionally, OPP supplementation resulted in improvement of total cholesterol and LDL-C levels, compared to the control treatment. The outcomes support our previous observations that OPP is safe and may have a protective role in reducing cholesterol levels.

Background Among the numerous well-documented medicinal herbs, Eurycoma longifolia (EL) has gained remarkable recognition due to its promising efficacy of stimulating bone formation in androgen-deficient osteoporosis. Though numerous animal studies have explored the bone-forming capacity of EL, the exact mechanism was yet to be explored. Objective(s) The present study was aimed to investigate the mechanism of bone-forming capacity of EL using MC3T3-E1 as an in vitro osteoblastic model. Materials and methods The cell differentiation capacity of EL was investigated by evaluating cell growth, alkaline phosphatase (ALP) activity, collagen deposition and mineralization. Taken together, time-mannered expression of bone-related mediators which include bone morphogenic protein-2 (BMP-2), ALP, runt-related transcription factor-2 (Runx-2), osteocalcin (OCN), type I collagen, osteopontin (OPN), transforming growth factor-β1 (TGF-β1) and androgen receptor (AR) were measured to comprehend bone-forming mechanism of EL. Results Results demonstrated a superior cell differentiation efficacy of EL (particularly at a dose of 25 μg/mL) that was evidenced by dramatically increased cell growth, higher ALP activity, collagen deposition and mineralization compared to the testosterone. Results analysis of the bone-related protein biomarkers indicated that the expression of these mediators was well-regulated in EL-treated cell cultures compared to the control groups. These findings revealed potential molecular mechanism of EL for the prevention and treatment of male osteoporosis. Conclusion The resulting data suggested that EL exhibited superior efficacy in stimulating bone formation via up-regulating the expression of various mitogenic proteins and thus can be considered as a potential natural alternative therapy for the treatment of osteoporosis., Graphical abstract Image 1

This review inspects all the available report on association of honey and the epithelial mesenchymal transition (EMT) event in wound healing. A systematic review of the literature was conducted to identify relevant studies on honey and EMT. The search was done in Medline via Ebscohost and Scopus database to obtained relevant articles published between 1823 and 2017. The main inclusion criteria were research articles published in English that reported changes in the EMT markers in in vitro wound healing model when subjected to honey. The literature search identified 19 potentially relevant articles, whereby 8 met the inclusion criteria. Two types of in vitro wound healing model were included, cutaneous and corneal wound. All studies reported a positive effect of honey in wound healing. In terms of EMT markers, honey was shown to upregulate mesenchymal markers and downregulated epithelial markers providing the evidence of EMT activation by honey. However, the effects on EMT varied dependent on the floral origin of the honey. This review provides good evidence that honey regulates the process of EMT and has a positive impact on wound healing.

Gymnema sylvestre is a plant included in Apocynaceae family and is located in many regions of Asia, Africa and Australia. This plant is widely used as a traditional therapy for different purposes. Even now it is being used as a dietary supplement due to its numerous therapeutic uses. It is known to have blood glucose lowering potential and, thus, is widely used in traditional and Ayurvedic systems of medicine. It renders glucose lowering activity due to the presence of phytochemicals, such as gurmarin, gymnemic acid as well as gymnemasaponins. Gymnema sylvestre is also known to have anti-oxidant, antibiotic, anti-inflammatory, antiviral, gastro and hepatoprotective, anticancer and lipid-lowering activities. This review discusses in details on different pharmacological and clinical potentials of Gymnema sylvestre and its chemical constituents associated with its therapeutic potentials.

Alcohol use disorder (AUD) is characterized by compulsive binge alcohol intake, leading to various health and social harms. Protein Kinase C epsilon (PKCe), a specific family of PKC isoenzyme, regulates binge alcohol intake and potentiates alcohol-related cues. Alcohol via upstream kinases like mammalian target to rapamycin complex 1 (mTORC1) or 2 (mTORC2), may affect the activities of PKCe or vice versa in AUD. mTORC2 phosphorylates PKCe at hydrophobic and turn motif, and mTORC2 was recently reported to be associated with alcohol seeking behavior, suggesting the potential role of mTORC2-PKCe interactions in pathophysiology of AUD. Mammalian target to rapamycin complex 1 (mTORC1), another form of mTOR complex regulates translation of synaptic proteins involved in alcohol-induced plasticity. Hence, in this article, we aimed to review the molecular composition of mTORC1 and mTORC2, drugs targeting PKCe, mTORC1, and mTORC2 in AUD, upstream regulation of mTORC1 and mTORC2 in AUD and downstream cellular mechanisms of mTORCs in pathogenesis of AUD.

The present review explored the anti-inflammatory and immunomodulatory properties of vitamin E, which has protective action against osteoporosis. A systematic review of the literature was conducted to identify the published bone studies on vitamin E. The studies included inflammatory or immunology-related parameters. Medline and Scopus databases were searched for relevant studies published from 2005 till 2015. Research articles published in English and confined to the effect of vitamin E on bone were included. It is pertinent to mention that these studies took into consideration inflammatory or immunology parameters including interleukin (IL)-1, IL-6, receptor activator of nuclear factor kappa-B ligand (RANKL), inducible nitric oxide synthases (iNOS), serum amyloid A (SAA), e-selection and high-sensitivity C-reactive protein (hs-CRP). An extended literature search yielded 127 potentially relevant articles with seven articles meeting the inclusion and exclusion criteria. Another recent article was added with the total number accounting to eight. All these included literature comprised five animal studies, one in-vitro study and two human studies. These studies demonstrated that vitamin E, especially tocotrienol, was able to alleviate IL-1, IL-6, RANKL, iNOS and hs-CRP levels in relation to bone metabolism. In conclusion, vitamin E exerts its anti-osteoporotic actions via its anti-inflammatory and immunomodulatory effects.

Ethnopharmacological relevance Eurycoma longifolia ( EL ) has been well-studied traditionally as a chief ingredient of many polyherbal formulations for the management of male osteoporosis. It has also been well-recognised to protect against bone calcium loss in orchidectomised rats. Aim of the study To evaluate the effects of EL on the time-mannered sequential proliferative, differentiative, and morphogenic modulation in osteoblasts compared with testosterone. Materials and methods Cell proliferation was analysed using MTS assay and phase contrast microscopy. Osteogenic differentiation of MC3T3-E1 cells was assessed through a series of characteristic assays which include crystal violet staining, alkaline phosphatase (ALP) activity and Van Gieson staining. Taken together, the bone mineralization of extra cellular matrix (ECM) was estimated using alizarin red s (ARS) staining, von kossa staining, scanning electron microscopic (SEM) and energy dispersive x-ray (EDX) analysis. Results The cell proliferation data clearly revealed the efficiency of EL particularly at a dose of 25 µg/mL, in improving the growth of MC3T3-E1 cells compared with the untreated cells. Data also showed the prominence of EL in significantly promoting ALP activity throughout the entire duration of treatment compared with the testosterone-treated cells. The osteogenic differentiation potential of EL was further explored by analysing mineralization data which revealed that the calcified nodule formation (calcium deposition) and phosphate deposition was more pronounced in cells treated with 25 µg/mL concentration of EL at various time points compared with the untreated and testosterone treated cells. The scanning electron microscopic (SEM) analysis also revealed highest globular masses of mineral deposits (identified as white colour crystals) in the ECM of cultured cells treated with 25 µg/mL concentration of EL. Conclusion Compared to testosterone, greater potential of EL in promoting the proliferation and osteogenic differentiation of MC3T3-E1 cells provides an in vitro basis for the prevention of male osteoporosis. Thus, we anticipate that EL can be considered as an alternative approach to testosterone replacement therapy (TRT) for the treatment of male osteoporosis.

Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined, neurodevelopmental disorder that has been modeled as a brain-based disease. The behavioral and cognitive features of ASD are associated with pervasive atypicalities in the central nervous system (CNS). To date, the exact mechanisms underlying the pathophysiology of ASD still remain unknown and there is currently no cure or effective treatment for this disorder. Many publications implicated the association of ASD with inflammation, immune dysregulation, neurotransmission dysfunction, mitochondrial impairment and cell signaling dysregulation. This review attempts to highlight evidence of the major pathophysiology of ASD including abnormalities in the brain structure and function, neuroglial activation and neuroinflammation, glutamatergic neurotransmission, mitochondrial dysfunction and mechanistic target of rapamycin (mTOR) signaling pathway dysregulation. Molecular and cellular factors that contributed to the pathogenesis of ASD and how they may affect the development and function of CNS are compiled in this review. However, findings of published studies have been complicated by the fact that autism is a very heterogeneous disorder; hence, we addressed the limitations that led to discrepancies in the reported findings. This review emphasizes the need for future studies to control study variables such as sample size, gender, age range and intelligence quotient (IQ), all of which that could affect the study measurements. Neuroinflammation or immune dysregulation, microglial activation, genetically linked neurotransmission, mitochondrial dysfunctions and mTOR signaling pathway could be the primary targets for treating and preventing ASD. Further research is required to better understand the molecular causes and how they may contribute to the pathophysiology of ASD.

Introduction Sexual dysfunction in hypertensive women is an often-neglected subject despite a reported prevalence of 42.1%. Although few reviews exist, a definitive relationship between hypertension and sexual dysfunction in women has not been clearly established. Aim To review the existing literature to definitively examine sexual dysfunction in women with hypertension, in both treated and untreated subjects. Methods We performed a systematic search for published literature of 3 electronic databases (Scopus, EBSCOhost Medline Complete, and Cochrane Library) in August 2018. The search terms with relevant truncation and Boolean were developed according to a population exposure-comparator-outcome model combining pilot searches. The quality of included studies was assessed with the McMaster Critical Review Form for Quantitative Studies. Initial search, limited to the English language, included a total of 2,198 studies. 31 studies (18,260 subjects) met our inclusion criteria and were included in the review. Sexual dysfunction in these studies was measured using different tools. We extracted information of study setting, country, number of subjects, participants’ age and blood pressure, comparators, and outcome. We ran a meta-analysis on the presence of sexual dysfunction as an outcome from the following comparisons: (i) hypertensive vs normotensive (ii) treated vs untreated hypertension, and (iii) exposure vs absence of specific class of anti-hypertensive drug. Main Outcome Measures Women with sexual dysfunction and hypertension were included. Results We found significant sexual dysfunction in women with hypertension compared with the normotensive group (pooled odds ratio [OR] = 2.789, 95% CI = 1.452–5.357, P = .002). However, there was no statistical difference of sexual dysfunction in women with treated or untreated hypertension (OR = 1.229, 95% CI = 0.675–2.236, P = .5). Treatment with alpha-/beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, and diuretics resulted in no statistical difference in sexual dysfunction in hypertensive women. Clinical Implications Because sexual dysfunction is prevalent in women with hypertension, it is imperative to address the underlying medical condition to manage this important clinical problem. Strength & Limitations Many studies had to be excluded from the meta-analysis, due to unavailability and incompleteness of data. Nevertheless, results of the review are useful to derive recommendations for alerting physicians of the need to routinely assess the sexual functioning of women with hypertension. Conclusion We conclude that women with hypertension are at increased risk for sexual dysfunction, and our findings imply that evaluation for sexual dysfunction needs to be part of the clinical management guidelines for women with hypertension.

Wound healing is a complex process of recovering the forms and functions of injured tissues. The process is tightly regulated by multiple growth factors and cytokines released at the wound site. Any alterations that disrupt the healing processes would worsen the tissue damage and prolong repair process. Various conditions may contribute to impaired wound healing, including infections, underlying diseases and medications. Numerous studies on the potential of natural products with anti-inflammatory, antioxidant, antibacterial and pro-collagen synthesis properties as wound healing agents have been performed. Their medicinal properties can be contributed by the content of bioactive phytochemical constituents such as alkaloids, essential oils, flavonoids, tannins, saponins, and phenolic compounds in the natural products. This review highlights the in vitro, in vivo and clinical studies on wound healing promotions by the selected natural products and the mechanisms involved.

Phytoestrogens have attracted considerable attention for their potential in the prevention of postmenopausal osteoporosis. Recently, a phytoestrogen-rich herbal plant, Marantodes pumilum var. alata (Blume) Kuntze was reported to protect against bone loss in ovariectomized rat. However, the bioactive compound responsible for these effects and the underlying mechanism were not known. Through bioassay-guided isolation, demethylbelamcandaquinone B (Dmcq B) was isolated and identified from Marantodes pumilum var. alata leaf extract. In terms of its bone anabolic effects, Dmcq B was at par with 17&beta, estradiol (E2), in promoting the proliferation, differentiation and mineralization of osteoblast cells. Dmcq-B increased early differentiation markers, collagen content and enzymatic ALP activity. It was demonstrated to regulate BMP2 signaling pathway which further activated the transcription factor, osterix. Subsequently, Dmcq B was able to increase the osteocalcin expression which promoted matrix mineralization as evidenced by the increase in calcium deposition. Dmcq B also reduced the protein level of receptor activator of NF-&kappa, &beta, ligand (RANKL) and promoted osteoprotegerin (OPG) protein expression by osteoblast cells, therefore hastening bone formation rate by decreasing RANKL/OPG ratio. Moreover, Dmcq B was able to increase ER expression, postulating its phytoestrogen property. As the conclusion, Dmcq B is the active compound isolated from Marantodes pumilum var. alata leaves, regulating osteoanabolic activities potentially through the BMP2 and ER signaling pathways.

Background: Gonadotropin releasing hormone (GnRH) antagonists may cause chemical castration in males by suppressing the pituitary-gonadal axis, hence reducing testosterone level. There are limited data on the effects of degarelix, a newer series of potent and long acting GnRH antagonist on bone. Objectives: The current study aimed at determining the effects of degarelix on bone turnover, bone densitometry, and bone mechanical strength in male rats. Methods: Eighteen male Sprague-Dawley rats were randomly divided into sham (SHAM), orchidectomized (ORX), and degarelix-induced (DGX) groups. Chemical castration was performed by subcutaneous degarelix injection (2 mg/kg) at the scapular region. The rats were scanned for baseline bone mineral area (BMA), bone mineral content (BMC), and bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA). Following six weeks of experimental period, BMA, BMC, and BMD were measured again with DXA and blood was collected for testosterone and bone biomarkers (osteocalcin and C-terminal of type I collagen crosslink (CTX-1)) measurements. The rats were euthanized and femora were dissected for bone biomechanical strength analysis. Results: Bilateral orchidectomy and degarelix administration significantly lowered serum testosterone level, decreased whole body BMC, femoral BMA, femoral BMC, and femoral BMD (P < 0.05) compared with the SHAM group. However, no significant changes were observed in bone biochemical markers and bone mechanical strength in all experimental groups. Conclusions: In conclusion, degarelix administration had comparable effects on bone as bilateral orchidectomy. Administration of degarelix provides an alternative method of inducing testosterone deficient-osteopenia in male rats without need for removing the testes.

BACKGROUND Eurycoma longifolia (EL) is a well-known aphrodisiac herb for men. Recently, the crude extract of EL was reported to possess anti-osteoporotic activities. OBJECTIVE This study aims to determine the bone protective effects of the standardized quassinoid-rich EL extract in testosterone-deficient rat model. METHODS Ninety-six intact male Sprague-Dawley rats were randomized into baseline, sham, orchidectomized, and chemically castrated groups. Chemical castration was performed via subcutaneous injection of degarelix at 2 mg/kg. The orchidectomized and degarelix-induced rats were administered with vehicle, intramuscularly injected with testosterone once a week, or orally supplemented with EL extract at doses of 25 mg/kg, 50 mg/kg or 100 mg/kg daily for 10 weeks. Bone mass, microarchitecture and strength were analyzed by dual-energy x-ray absorptiometry (DEXA), micro-CT and three-point bending test. RESULTS Whole body bone mineral density and femoral bone mineral content significantly increased in testosterone groups (p < 0.05). Micro-CT analysis revealed that trabecular bone volume, number, separation and connectivity density were significantly improved by testosterone administration. However, the structural model index was only improved in degarelix group supplemented with 100 mg/kg EL extract (P < 0.05). The improvement of cortical thickness by EL extract was similar to that of testosterone groups (p < 0.05). Biomechanically, EL extract supplementation was able to improve stiffness, strain and modulus of elasticity in degarelix-induced groups, while stress parameter was significantly improved in orchidectomized groups (p < 0.05). CONCLUSION Quassinoid-rich EL extract enables to protect against bone loss due to testosterone deficiency. The protective effect on cortical thickness and biomechanical parameters is comparable to testosterone group.