In recent biomedical research, the area of cancer and infectious diseases has a leading position in the utilization of medicinal plants as a source of drug discovery. Malaysia has a diversity and a large number of underutilized fruits that are rich in phenolic compounds. Artoarpus altilis consider an underutilized fruit that is rich in phenolic compounds. Methanol extracts of A. altilis have been previously found to contain a high content of antioxidant phytochemicals. The purpose of the study was to evaluate the cytotoxicity and toxicological effect of methanol fruit extracts against MCF-7 cells. To determine the least concentration that might kill or suppress the growth of the cancer cells was in a concentration-dependent manner approach. The variation in the cytotoxic activity among the extracts was indicated by determining the IC50 of each extract against cells at 72 h. The IC50 of the samples was measured using a trypan blue exclusion assay. The methanol extract of the pulp part showed the least inhibition concentration of 15.40±0.91 μg/mL on MCF-7 cells. In the study, the molecular mechanism of methanol extracts-induced apoptosis and cell cycle arrested in human cancer cells were investigated in a time-dependent-manners approach by using flow cytometry. The treated cells were stained with nexin to detect early and late apoptosis and with propidium iodide (PI) for cell cycle arrest associated with the DNA fragmentation, various cell arrests occurred at G1/S, S, and G2/M phases. Lastly, the gene expression analysis by (RT-qPCR) method was carried out by analyzing the expression of the gene of interest for the quantification of mRNA levels. Results after cells treated with IC50 were revealed by upregulating anti-apoptotic genes/downregulated of pro-apoptotic BCL-2 gene expressions were triggered the treated cells into CASPASE-3, intrinsic and extrinsic pathways. These findings suggest that the methanol extracts of three parts of A. altilis fruit have potential anticancer activity against MCF-7 cells mainly the pulp part of the fruit.
The coronavirus disease 2019 (COVID-19) pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities.
Malaysia has achieved reasonable health outcomes even though the country spends a modest amount of Gross Domestic Product on healthcare. However, the country is now experiencing a rising incidence of both infectious diseases and chronic lifestyle conditions that reflect growing wealth in a vibrant and successful economy. With an eye on an ageing population, reform of the health sector is a government priority. As in other many parts of the world, general practitioners are the first healthcare professional consulted by patients. The Malaysian health system is served by public and private care providers. The integration of the two sectors is a key target for reform. However, the future health of the nation will depend on leadership in the primary care sector. This leadership will need to be informed by research to integrate care providers, empower patients, bridge cultural gaps and ensure equitable access to scarce health resources.
Henipaviruses are implicated in severe and frequently fatal pneumonia and encephalitis in humans. There are no approved vaccines or treatments available for human use, and testing of candidates requires the use of well-characterized animal models that mimic human disease. We performed a comprehensive and statistically-powered evaluation of the African green monkey model to define parameters critical to disease progression and the extent to which they correlate with human disease. African green monkeys were inoculated by the intratracheal route with 2.5 × 10(4) plaque forming units of the Malaysia strain of Nipah virus. Physiological data captured using telemetry implants and assessed in conjunction with clinical pathology were consistent with shock, and histopathology confirmed widespread tissue involvement associated with systemic vasculitis in animals that succumbed to acute disease. In addition, relapse encephalitis was identified in 100% of animals that survived beyond the acute disease phase. Our data suggest that disease progression in the African green monkey is comparable to the variable outcome of Nipah virus infection in humans.
Developing new treatments for emerging infectious diseases in infectious and noninfectious diseases has attracted a particular attention. The emergence of viral diseases is expected to accelerate; these data indicate the need for a proactive approach to develop widely active family specific and cross family therapies for future disease outbreaks. Viral disease such as pneumonia, severe acute respiratory syndrome type 2, HIV infection, and Hepatitis-C virus can cause directly and indirectly cardiovascular disease (CVD). Emphasis should be placed not only on the development of broad-spectrum molecules and antibodies but also on host factor therapy, including the reutilization of previously approved or developing drugs. Another new class of therapeutics with great antiviral therapeutic potential is molecular communication networks using deep learning autoencoder (DL-AEs). The use of DL-AEs for diagnosis and prognosis prediction of infectious and noninfectious diseases has attracted a particular attention. MCN is map to molecular signaling and communication that are found inside and outside the human body where the goal is to develop a new black box mechanism that can serve the future robust healthcare industry (HCI). MCN has the ability to characterize the signaling process between cells and infectious disease locations at various levels of the human body called point-to-point MCN through DL-AE and provide targeted drug delivery (TDD) environment. Through MCN, and DL-AE healthcare provider can remotely measure biological signals and control certain processes in the required organism for the maintenance of the patient's health state. We use biomicrodevices to promote the real-time monitoring of human health and storage of the gathered data in the cloud. In this paper, we use the DL-based AE approach to design and implement a new drug source and target for the MCN under white Gaussian noise. Simulation results show that transceiver executions for a given medium model that reduces the bit error rate which can be learned. Then, next development of molecular diagnosis such as heart sounds is classified. Furthermore, biohealth interface for the inside and outside human body mechanism is presented, comparative perspective with up-to-date current situation about MCN.
Foodborne illness is recognized as an emerging infectious disease. The incidence of foodborne
infections is common and the majority cases are undiagnosed or unreported. Apart from some
diarrhea or minor gastrointestinal problem, some foodborne pathogenic microbes may cause
death, particularly to those people with weakened immune system. In this study, we have
developed a new fermented papaya beverage using symbiotic culture of yeast and acetic acid
bacteria under controlled biofermentation process. An in-vitro assessment of fermented papaya
beverage against few foodborne pathogenic microorganism was conducted to determine
its minimum bactericidal concentration (MBC>99). Three types of foodborne pathogen:
Escherichia coli O157, Salmonella enterica serovar Typhimurium ATCC 53648, Salmonella
enterica serovar Enteritidis (isolated from infectious chicken) were selected. From minimum
bactericidal concentration (MBC>99) assay, both fermented papaya pulp and leaves beverages
have shown 100% killing rate against three selected foodborne pathogenic microbes. Inversely,
non-fermented papaya pulp and leaves beverages indicated no inhibition at all. In fact, further
dilution of fermented papaya pulp and leaves beverages demonstrated different degree of
MBC>99 and brix value, but the pH value remained less than 3.5. These findings indicated
the combination of soluble solid compounds presents in both fermented papaya beverage and
product acidity play an important role in the inhibition of pathogenic microorganisms. The
preliminary promising results of this work have shown that the great potential of fermented
papaya beverages as a preventive measure to reduce the incidence of foodborne illness.
Biofilms are a collective of multiple types of bacteria that develop on a variety of surfaces. Biofilm development results in heightened resistance to antibiotics. Quorum sensing plays an important role in biofilm development as it is one of the common communication mechanisms within cells, which balances and stabilizes the environment, when the amount of bacteria increases. Because of the important implications of the roles biofilms play in infectious diseases, it is crucial to investigate natural antibacterial agents that are able to regulate biofilm formation and development. Various studies have suggested that natural plant products have the potential to suppress bacterial growth and exhibit chemopreventive traits in the modulation of biofilm development. In this review, we discuss and collate potential antibiofilm drugs and biological molecules from natural sources, along with their underlying mechanisms of action. In addition, we also discuss the antibiofilm drugs that are currently under clinical trials and highlight their potential future uses.
Natural disasters may lead to infectious disease outbreaks when they result in substantial population displacement and exacerbate synergic risk factors (change in the environment, in human conditions and in the vulnerability to existing pathogens) for disease transmission. We reviewed risk factors and potential infectious diseases resulting from prolonged secondary effects of major natural disasters that occurred from 2000 to 2011. Natural disasters including floods, tsunamis, earthquakes, tropical cyclones (e.g., hurricanes and typhoons) and tornadoes have been secondarily described with the following infectious diseases including diarrheal diseases, acute respiratory infections, malaria, leptospirosis, measles, dengue fever, viral hepatitis, typhoid fever, meningitis, as well as tetanus and cutaneous mucormycosis. Risk assessment is essential in post-disaster situations and the rapid implementation of control measures through re-establishment and improvement of primary healthcare delivery should be given high priority, especially in the absence of pre-disaster surveillance data.
The present issue brings a diverse yet interesting array of research, but they all have a common thread-they answer to a clinical problem raised. The topics span human sexuality, diagnostic challenges, sports medicine, nosocomial infections, screening for neonatal infections, statistical analysis and fine-tuning the art of anaesthesia.(Copied from article).
Antibody phage display is regarded as a critical tool for the development of monoclonal antibodies for infectious diseases. The different classes of antibody libraries are classified based on the source of repertoire used to generate the libraries. Immune antibody libraries are generated from disease infected host or immunization against an infectious agent. Antibodies derived from immune libraries are distinct from those derived from naïve libraries as the host's in vivo immune mechanisms shape the antibody repertoire to yield high affinity antibodies. As the immune system is constantly evolving in accordance to the health state of an individual, immune libraries can offer more than just infection-specific antibodies but also antibodies derived from the memory B-cells much like naïve libraries. The combinatorial nature of the gene cloning process would give rise to a combination of natural and un-natural antibody gene pairings in the immune library. These factors have a profound impact on the coverage of immune antibody libraries to target both disease-specific and non-disease specific antigens. This review looks at the diverse nature of antibody responses for immune library generation and discusses the extended potential of a disease-specified immune library in the context of phage display.
Many countries neighboring Malaysia have reported human infections by chikungunya virus, a mosquito-borne togavirus belonging to the genus Alphavirus. However, although there is serological evidence of its presence in Malaysia, chikungunya virus has not been known to be associated with clinical illness in the country. An outbreak of chikungunya virus occurred in Klang, Malaysia, between December 1998 and February 1999. The majority of the cases were in adults and the clinical presentation was similar to classical chikungunya infections. Malaysia is heavily dependent on migrant workers from countries where chikungunya is endemic. It is speculated that the virus has been re-introduced into the country through the movement of these workers.
Emerging and re-emerging infectious diseases have become a major global problem. Malaysia appears to be an epicenter for such infections and in recent years, several outbreaks have occurred resulting in loss of lives and economic hardships. In this paper, we discussed the outbreaks of leptospirosis, enterovirus 71 encephalitis, chikungunya polyarthritis and Nipah encephalitis and how a developing country such as Malaysia managed the situation with the help of international agencies and organisations. Many valuable lessons were learned and by sharing our experience, it is hoped that we will be in a better position to handle future outbreaks and prevent their spread to countries in the region.
The conventional susceptible-infectious-recovered (SIR) model tends to magnify the transmission dynamics of infectious diseases, and thus the estimated total infections and immunized population may be higher than the threshold required for infection control and eradication. The study developed a new SIR framework that allows the transmission rate of infectious diseases to decline along with the reduced risk of contact infection to overcome the limitations of the conventional SIR model. Two new SIR models were formulated to mimic the declining transmission rate of infectious diseases at different stages of transmission. Model A utilized the declining transmission rate along with the reduced risk of contact infection following infection, while Model B incorporated the declining transmission rate following recovery. Both new models and the conventional SIR model were then used to simulate an infectious disease with a basic reproduction number (r0) of 3.0 and a herd immunity threshold (HIT) of 0.667 with and without vaccination. Outcomes of simulations were assessed at the time when the total immunized population reached the level predicted by the HIT, and at the end of simulations. Further, all three models were used to simulate the transmission dynamics of seasonal influenza in the United States and disease burdens were projected and compared with estimates from the Centers for Disease Control and Prevention. For the simulated infectious disease, in the initial phase of the outbreak, all three models performed expectedly when the sizes of infectious and recovered populations were relatively small. As the infectious population increased, the conventional SIR model appeared to overestimate the infections even when the HIT was achieved in all scenarios with and without vaccination. For the same scenario, Model A appeared to attain the level predicted by the HIT and in comparison, Model B projected the infectious disease to be controlled at the level predicted by the HIT only at high vaccination rates. For infectious diseases with high r0, and at low vaccination rates, the level at which the infectious disease was controlled cannot be accurately predicted by the current theorem. Transmission dynamics of infectious diseases with herd immunity can be accurately modelled by allowing the transmission rate of infectious diseases to decline along with the reduction of contact infection risk after recovery or vaccination. Model B provides a credible framework for modelling infectious diseases with herd immunity in a randomly mixed population.
OBJECTIVE: To study the etiology, outcome and prognostic indicators in children with fulminant hepatic failure in the United Kingdom.
DESIGN: Retrospective review of all patients <17 years with fulminant hepatic failure from 1991 to 2000. Fulminant hepatic failure was defined as presence of coagulopathy (prothrombin time >24 seconds or International Normalized Ratio >2.0) with or without hepatic encephalopathy within 8 weeks of the onset of symptoms.
SETTING: Liver Unit, Birmingham Children's Hospital, United Kingdom.
RESULTS: Ninety-seven children (48 male, 49 female; median age, 27 months; range, 1 day-192.0 months) were identified with fulminant hepatic failure. The etiologies were: 22 metabolic, 53 infectious, 19 drug-induced, and 3 autoimmune hepatitis. The overall survival rate was 61%. 33% (32/97) recovered spontaneously with supportive management. Fifty-five children were assessed for liver transplantation. Four were unstable and were not listed for liver transplantation; 11 died while awaiting liver transplantation. Liver transplantation was contraindicated in 10 children. Of the 40 children who underwent liver transplantation, 27 survived. Children with autoimmune hepatitis, paracetamol overdose or hepatitis A were more likely to survive without liver transplantation. Children who had a delay between the first symptom of liver disease and the onset of hepatic encephalopathy (median, 10.5 days versus 3.5 days), higher plasma bilirubin (299 micromol/L versus 80 micromol/L), higher prothrombin time (62 seconds versus 40 seconds) or lower alanine aminotransferase (1288 IU/L versus 2929 IU/L) levels on admission were more likely to die of fulminant hepatic failure or require liver transplantation (P < 0.05). On multivariate analysis, the significant independent predictors for the eventual failure of conservative therapy were time to onset of hepatic encephalopathy >7 days, prothrombin time >55 seconds and alanine aminotransferase =2384 IU/L on admission.
CONCLUSIONS: Children with fulminant hepatic failure with severe coagulopathy, lower alanine aminotransferase on admission and prolonged duration of illness before the onset of hepatic encephalopathy are more likely to require liver transplantation. Early referral to a specialized center for consideration of liver transplantation is vital.
Vaccines, used appropriately and efficiently, have changed the landscape of infectious diseases. Poliomyelitis is almost completely eliminated globally. In many industrialised countries, there has been over 99 percent reduction in incidence of diphtheria, tetanus, measles, mumps, rubella, Haemophilus in-fluenzae b meningitis and over 97 percent reduction in whooping cough.',2Unlike anti-biotics, most vaccines have remained equally effective despite years of continuous usage.
Tuberculosis (TB) is a chronic inflammatory and zoonotic disease caused by Mycobacterium tuberculosis complex (MTBC) members, which affects various domestic animals, wildlife, and humans. Some wild animals serve as reservoir hosts in the transmission and epidemiology of the disease. Therefore, the monitoring and surveillance of both wild and domestic hosts are critical for prevention and control strategies. For TB diagnosis, the single intradermal tuberculin test or the single comparative intradermal tuberculin test, and the gamma-interferon test, which is regarded as an ancillary test, are used. Postmortem examination can identify granulomatous lesions compatible with a diagnosis of TB. In contrast, smears of the lesions can be stained for acid-fast bacilli, and samples of the affected organs can be subjected to histopathological analyses. Culture is the gold standard test for isolating mycobacterial bacilli because it has high sensitivity and specificity compared with other methods. Serology for antibody detection allows the testing of many samples simply, rapidly, and inexpensively, and the protocol can be standardized in different laboratories. Molecular biological analyses are also applicable to trace the epidemiology of the disease. In conclusion, reviewing the various techniques used in MTBC diagnosis can help establish guidelines for researchers when choosing a particular diagnostic method depending on the situation at hand, be it disease outbreaks in wildlife or for epidemiological studies. This is because a good understanding of various diagnostic techniques will aid in monitoring and managing emerging pandemic threats of infectious diseases from wildlife and also preventing the potential spread of zoonotic TB to livestock and humans. This review aimed to provide up-to-date information on different techniques used for diagnosing TB at the interfaces between wildlife, livestock, and humans.
The health of a population and the development of health services in a country at a particular time in history are directly linked to the socioeconomic system. This paper discusses health and health services in Malay Peninsula during the time that it was a British colony. Economic production under British colonialism, which is basically a capitalist system, is organized primarily for the purpose of realizing profits. The health of the population is in direct conflict with and generally subordinated to this main objective. The pattern of health that emerges reflects this general framework. Moreover, health services under the colonialist system are developed primarily to serve the economic interests of the colonialists. Hence, the structure of health services is biased toward curative medicine and centered mainly in the urban areas.
On review of 3117 patients' records (all were female Indonesian foreign workers over the span of eight years (1997 to 2004 in a private clinic in Johor Bahru, 223 cases (7.2%) were found to have various medical problems. These 3117 foreigners were to be employed as domestic helpers in Malaysia. They were examined upon arrival in Johor Bahru even though our government did not require this pre-requisite (before 1st August 2005) as they were examined and certified fit in their country of origin before embarking to Malaysia. The proportion of female Indonesian foreign workers who were afflicted with category 1 conditions was 55.6% (which rendered them unfit for employment) and category 2 conditions was 44.4%. The medical problem detected most frequently was hypertension. Sixty-one (80.3%) out of 76 workers had stage 2 hypertension (JNC 7 report). Pulmonary tuberculosis ranked second in this review and is a category 1 condition. This paper supports the recent move by the Malaysian Ministry of Health to implement mandatory medical examinations for all foreign workers arriving in Malaysia within one month of arrival regardless of whether or not they are certified fit in their countries of origin.