COVID-19 patients with hypertension have more severe disease: a multicenter retrospective observational study

COVID-19 patients with hypertension have more severe disease: a multicenter retrospective observational study

Late last year, a number of unexplained pneumonia cases surfaced in Wuhan, China. Later scientists revealed that it is caused by a familiar group of pathogens, coronavirus. The WHO later named this virus, COVID-19. The virus is highly contagious, infecting millions in the last couple of months.

From previous studies, it is considered that angiotensin-converting enzyme (ACE2) is the receptor for the COVID-19 virus to enter the host cell. ACE2 is a widely expressed receptor in several organ systems of the human body, including cardiovascular and respiratory systems. The enzyme helps in catalyzing angiotensin II to angiotensin 1-7, which is the peptide counteracting proinflammation caused by Angiotensin II. 

Studies have proven that hypertension is a common condition that co-occurs in patients with COVID-19. A previously conducted study, involving 1099 COVID-19 patients reported that 23.4% of the population also suffered from hypertension. Due to the coexisting status of hypertension and COVID-19 and the involvement of ACE2 in hypertension, the authors of this study speculate that hypertension may directly be involved with the pathogenesis of COVID-19. 

To confirm if hypertension affects the progress and prognosis of COVID-19, the published study was conducted. The study involved 310 patients from the Central Hospital of Wuhan and Wuhan Jinyintan Hospital. All the participants according to the WHO were tested positive for COVID-19. The study was later divided according to high blood pressure (hypertensive and non-hypertensive group). To avoid unwanted complications, the hypertension group was further segregated to exclude patients with other complications other than hypertension. 

All the participants were monitored closely and the entire course of the disease was recorded. The median age of the participants in the study was 62 years and the prevalence rate of hypertension was 36.5%. The authors speculate that the high prevalence rate of hypertension in the study group could be due to the high median age. The study also revealed that COVID-19 patients with high blood pressure showed higher mortality. 

Evidence suggests that an imbalance of cytokines could be a possible correlation between COVID-19 and hypertension. An increase in cytokines like IL-6, IL-7, and tumor necrosis factor is associated with the development of hypertension. It should also be noted that the increased levels of cytokines, may potentially activate excessive inflammatory reactions, resulting in cell and lung damage. 

Overall the comparative study conducted using COVID-19 patients with and without hypertension showed that patients who were hypertensive were more likely to be severely affected with COVID-19 compared to the non-hypertensive group. It must be brought to light that there might be a small number of people with hypertension not recorded because the diagnosis of hypertension in this study was extracted from medical history data. 

Finally, the authors conclude that much larger groups need to be studied since the current result could be due to the higher aged participants. In the future, additional complications also need to be analyzed like ARDS, renal injury focusing on its risks associated with hypertension and COVID-19. 

Source

Risk Factors and Biomarkers of Ischemic Stroke in Cancer Patients

Risk Factors and Biomarkers of Ischemic Stroke in Cancer Patients

Numerous types of cancer are associated with ischemic stroke and are popularly known to be co-morbid conditions. They are two of the most frequent causes of death among the elderly population. A previous report of autopsies on cancer patients indicated that around 7.4% of the population suffered from stroke symptoms. With further analysis it was noticed that about 3.5% of the cancer patients were paralysed from strokes. 

The causes of ischemic stroke in cancer and non-cancer patients are highly different. Reports suggest, most of the cancer patients suffer from stroke mainly due to hypercoagulation. The blood clot formed restricts the blood flow to the brain, causing the cells in the brain to perish. This in turn paralyses the parts of the body controlled by the dead cells. While on the other hand, some reports suggest that stroke and cancer pathogenesis may be due to coagulopathy and atherosclerosis. The aim of this study is to study ischemic stroke in cancer patients using relevant biomarkers and compare it with non cancer patients with stroke. 

The study involved cancer patients with ischemic stroke from General Hospital in Busan, Korea. All the patients had active cancer with an onset of stroke symptoms. The control group used were patients from the same hospital, non cancer patients suffering from ischemic stroke. For examining the biomarkers, patients’ blood was collected and serum was assessed. 

The study found that biomarkers such as D-dimer levels, erythrocyte sedimentation rate (ESR), fibrinogen and Brain natriuretic peptide (BNP) were significantly higher in the cancer patients when compared to non cancer patients with stroke. 

D-dimer are one of the basic bio-markers for stroke due to their discovery as by-products of fibrinolysis. As a fibrin degradation product, dimer is directly associated with coagulation and plays a major role in hypercoagulation. Compared to non cancer ischemic stroke patients, D-dimer levels were found to be higher in cancer patients diagnosed with stroke. 

Blood coagulation in cancer patients is activated by inflammation. In this study, the authors used ESR, because of its well known use as a marker for infection and inflammation. An increased level of ESR indicating fibrinolysis was noticed in cancer stroke patients when compared to the control group.

From previous papers, it is well known that fibrinogen plays a major role in inflammation and platelet aggregation. An increase in fibrinogen is directly associated with increased risk of stroke in patients. In the current study cancer patients with ischemic stroke had a significant increase in fibrinogen than non cancer patients. 

Cancer patients with ischemic stroke portrayed high levels of stroke biomarkers when compared to the non cancer patients with ischemic stroke- control group. The above results showcase a strong relationship between the cancer patients and conditions like hypercoagulation and inflammation, which could possibly explain the frequency of paralysis in aged cancer patients leading to death. Therefore, in order to reduce any incidence of ischemic stroke in cancer patients, doctors should focus on reducing inflammation and platelet coagulation. 

Source

Adapting to survive: How Candida overcomes host-imposed constraints during human colonization

Adapting to survive: How Candida overcomes host-imposed constraints during human colonization

The human body is well known to host a large number of microbes, mostly harmless but when triggered might turn virulent. A large fungal ecosystem resides inside a human body mainly including Candida species, constituting a large part of the human body’s microbial flora. Usually asymptomatic, Candida forms small colonies, but when triggered such as environmental change, can potentially help the microbes to break barriers and cause life-threatening diseases.

Though multiple numbers of antifungal drugs are available, it is recently found that Candida species is capable of building resistance against the drugs by forming biofilms. The article further talks about the environment within the host body paving way to such resistance. 

Within the human host, Candida is capable of changing morphology and functions according to the change in the environment it resides in. Several factors play a role including temperature, ph, and oxygen supply. Candida depending on the environment can take forms such as hyphae, budding, or even pseudohyphae. 

Another crucial role played in a microbial existence within the human host is nutrients availability. It is reported that microbes thrive in the area of high glucose content. When deprived of glucose is when microbes turn to another source of nonfermentable nutrients. Research performed in labs using Candida flora has reported that in the presence of glucose the microbe is known to morph into hyphae and promote antifungal resistance. 

The limitations of micronutrients such as iron magnesium, and copper are known to limit the growth of invading microbes. But this is quite tricky as micronutrients are needed both by the host and microbes in functioning such as biochemical and cellular functions. 

It is very well known that oxygen and ph levels vary within every niche in the human body. While some are alkaline and high on oxygen concentration others are hypoxic and acidic. Candida microbes being versatile they are, can adapt their cell walls according to the change in ph. It is also interesting to note that Candida microbes thrive under hypoxic conditions, inducing their hyphal growth and causing immune evasion. 

The above has described the flexibility of the microbes to overcome multiple constraints faced in the host body. This ability of Candida helps it to form colonies and invade niches around the body. Another strategy imparted by the microbes is biofilm formation against the host body or biomedical devices. Biofilms consist of a 3D community of adherent cells with different biological properties. These cells are embedded in the ECM, which helps in maintaining the overall integrity of the biofilm. The ECM also acts as a protective barrier against any drug invasion. These features play a crucial role in Candida microbes resistance against antifungals and biomedical devices. 

With the emergence of resistant Candida species, the need to develop new antifungals is inevitable. Research using an in vivo model to mimic the host conditions is giving close insights to unravel the mysteries of the microbes. These approaches are paving the way to novel therapeutic vaccines and anti-fungal treatments, enhancing the body’s ability to fight off the infections. 

Source

Artificial intelligence-enabled rapid diagnosis of patients with COVID-19

Artificial intelligence-enabled rapid diagnosis of patients with COVID-19

Since December 2019, multiple cases of pneumonia due to unknown reasons have emerged in Wuhan, China. Through testing multiple patient samples, scientists extrapolated a new coronavirus termed COVID-19. With no FDA approved therapeutics or treatment available for the disease, diagnosis plays an important role in containing COCVID-19, giving a path to the rapid implementation of control measures to limit the spread. With the disease spreading to almost 100 countries, a million cases have been confirmed worldwide to date. Imaging is one of the main principles used in diagnosing and evaluating the disease, with the final diagnosis depending on reverse transcriptase-polymerase chain reaction (RT-PCR). 

In response to the growing number of COVID-19 cases, there is currently a shortage of diagnostic kits worldwide. Multiple industries are coming forward to develop rapid, easy to use diagnostic kits to facilitate testing. However before these kits can be commercialized, they must be tested and validated. With the current available tests taking almost 2 days to complete and produce a result, serial testing is required to rule out any negative cases. Additionally, it is a mystery as to whether an RT-PCR is a gold standard and whether a false positive/ negative result is common. The above reasons highlight the need for alternative testing methods to produce rapid and accurate results to identify, isolate, and treat the affected people. 

Chest computed tomography is also a much-used valuable component in testing COVID-19. With some of the patients showing early-stage symptoms in radiological finding, limits the CT ability to differentiate between a positive and negative case. In this current study, the authors have used Artificial Intelligence (AI) algorithms to help in integrating CT scanning in finding the symptoms of the virus, exposure history and reliable lab testing to rapidly diagnose the patients affected with COVID-19. 

A trial was performed on 905 patients diagnosed using RT-PCR and next-generation RT-PCR and around 46% (419) people were declared positive for COVID-19. Parallelly in a test set of 279 participants, the AI system managed to achieve accuracy to about 92% of the population and had equal or even better sensitivity than a senior radiologist. The AI system also improved the detection of COVID-19 positive patients with negative CT scans, identifying 17 out of 25 participants who were tested positive via RT-PCR but negative with normal CT scans. In comparison, the radiologists’ declared the said 17 participants to be COVID negative. 

AI shows signs of analyzing huge amounts of data quickly, a quality that is much needed in the current pandemic. A major limitation of the above study is the small sample size, with available CT scans and clinical history data, the AI system can help in diagnosing COVID-19 patients rapidly. Though a promising tool, further data collection is required to test the generalization of AI mapping on other patient populations.

Source

Transient expression of a green fluorescent protein in tobacco and maize chloroplast

Maize is considered to be one of the staple crops across the world. However, the limited production and unforeseen weather conditions often limit its availability. This is the major reason that scientists across the globe are working towards finding ways to improve the stability of the maize crop in harsh environmental conditions and its overall production rate. The improved quality of maize will not only help meet the demand of the ever-growing global population but will also overcome the shortage due to unanticipated environmental conditions. To achieve this, researchers tried for maize plastid transformation, which is not achieved effectively yet due to the recalcitrant conditions of the crop.

In the present study, researchers constructed two vectors containing homologous recombination sequences from maize and grass. These vectors are designed to later integrate into the chloroplast genome from an inverted repeat region. The vectors consist of two crucial genes mgfp5 and hph gene (as selection marker). The former gene is driven by Prrn, a leader sequence of the atpB gene and a terminator sequence from the rbcL gene. Whereas the later is driven by Prrn, a leader sequence from rbcL gene and a terminator sequence from the rbcL gene. The vectors were then used to transform the explants of maize, tobacco, and E.coli to assess the transitory expression. The expression levels were evident from the green and red fluorescent light when observed under the epiflourescence microscope.

The results of the study show the successful expression of both vectors, along with the presence of a reporter gene in all three organisms. This highlights the capability of vectors to express genes in the cell compartments. The results in the paper are the first report of transient expression of GFP in maize embryos, offering the opportunity to improve the recalcitrant crops genetically using biotechnological interventions. 

An in situ-Synthesized Gene Chip for the Detection of Food-Borne Pathogens on Fresh-Cut Cantaloupe and Lettuce

Food-borne pathogens are one of the major reasons behind endangering the life and safety of people across the globe. Fresh foods are specifically more vulnerable to these pathogens, making it crucial to have a very efficient food safety surveillance technology. The development of such technology will help in offering rapid detection of food-borne pathogens. In the present study, researchers developed an In-situ synthesized gene chip for the detection of the food-borne pathogen. Here the researchers first identified and screened the target genes by comparing the sequences of common food-borne pathogens like Salmonella, Vibrio parahemolyticus, Staphylococcus Aureus, Listeria monocytogenes and E.coli 0157:H7 from the NCBI database. Unique tilling array probes were designed that helps to target the selected genes in an optimized hybridization system. The resultant assay showed high specificity along with strong amplification signals. The results were highly accurate with a detection limit of approximately 3 log cfu/g without culturing. The detection time for the five target food-borne pathogens on the fresh-cut cantaloupe and lettuces was found to be 24 hours. This highlights the great efficacy of the detection system to rapidly monitor the pathogens on the fresh food items. Such a system can be easily incorporated as an efficient food surveillance system for checking the logistical distribution chain, the food at the processing stage, cleaning condition at the food manufacturing plants, transport, sales and more. The technology is considered valuable as it supports the safety of fresh agricultural products, reducing the overall wastage of food due to infectious pathogens.

COVID 19: A battle between heat and humidity Vs Sunshine

Enhanced Thermostability and Anticancer Activity in Breast Cancer Cells of Laccase Immobilized on Pluronic-Stabilized Nanoparticles

Laccases are mainly found in fungi and plants known for catalyzing oxidation reactions. They are often named as multi-copper enzymes having a wide range of applications across a multitude of biotechnological processes.  Though widely used the major challenge is the low stability of the free enzyme which often restricts its usability for industrial purposes.  The development of new methods that can enhance the enzymatic activity is a need of time. In the present study, immobilization of trametes versicolor laccase on pH-responsive, pluronic stabilized silver nanoparticles (AgNPsTrp) was carried out. The results showed enhanced activity if enzyme upon stabilization of AgNPsTrp with amphiphilic copolymer Pluronic F127, this helps in changing the microenvironment of active site facilitating the improved activity. The results were confirmed using circular dichroism (CD) and fluorescence spectroscopy. Further analysis showed that lowering the activation energy and expanding the temperature window for substrate hydrolysis can play a crucial role in improving the enzyme activity. No change in the behavior of the nanocomposite indicated the stability of the enzyme as normal with the absence of any aggregation after immobilization. The efficiency of the nanocomposite in breast cancer cells- MCF-7 was observed which showed inhibition of cell proliferation by promoting cell apoptosis and beta-estradiol degradation. Further, qRT- PCR experiments were conducted to understand the underlying molecular mechanism hindering cell proliferation. The analysis showed a reduced level of mRNA levels of the anti-apoptotic genes and enhancement in level of pro-apoptotic genes. For example, BCL-2 and NF-kβ, and increase in levels of pro-apoptotic genes like p53. The entire study provides a new way of enhancing the enzymatic activity of Laccases and extending its subsequent applications.

Source

Cellulase and xylanase synergism in industrial biotechnology

Cellulase and Xylanase synergism in industrial biotechnology

In recent years, many studies have been carried out which shows tremendous benefits of biocatalyst when compared to chemical catalysts. Biocatalyst helps in carrying out reactions in an environment-friendly manner while providing a high level of selectivity, specificity, and low energy consumption.  Two of the most widely used enzyme as biocatalyst are cellulose and xylanase wherein the former is considered to be the 3rd highest used enzyme. Many of the industrial applications require the use of both the enzyme in combination such as bioethanol production, removal of ink in waste paper industries, food processing industries, feed processing, removal of fibers from the textile materials, pulp production, pharmaceuticals and many more. Cellulose and xylanase are mainly produced by microorganisms which increases the demands of these microorganisms in the market. In this review, are discussing the synergistic application of both cellulose and xylanase enzyme as biocatalyst in various industries. Besides this, the paper also discusses the potential applications and requirements of microbial systems producing such enzymes. The paper highlights the future prospects associated with the further development of these enzymes as a coherent part of various industrial processes.

Source

Antibodies Targeting Influenza Viruses – A Hope for Universal Vaccine

Succession of physiological stages hallmarks the transcriptomic response of fungus Aspergillus niger to lignocellulose

Gaining insights about the mechanism of lignocellulose degradation by fungi is one of the pathbreaking discoveries for renewable-based biotechnology, specifically for the production of hydrolytic enzymes. Many detailed studies are available which evaluates fungal degradation when the expression levels of CAZyme reach its peak. However, the basic understanding of how fungi survive on lignocelluloses is still under the pipeline. This paper uses Aspergillus niger to explore its responses against six different substrates playing role in biofuel production. The responses to Miscanthus were compared with wheat straw, in isolation and in combination with ionic & hydrothermal feedstock pretreatment.  A metabolic model is mapped using a thorough evaluation of genome-wide transcriptome in combination with defined targeted transcripts and protein analyses. The exposure to different substrates showed enhancement in fatty acid oxidation and lipid metabolism transcripts. Strains with deletion of farA (ortholog of the fatty acid beta-oxidation transcriptional regulator) showed the reduced expression level of genes encoding lignocelluloses degradative CAZyme, indicating the role of beta-oxidation in mediating the adaptation to lignocelluloses. Activation of novel secondary metabolite gene clusters was noticed at the later life stages which are of great consideration due to their importance in synthesis of bioactive compounds. The entire study highlights that substrate composition and structure influence plays a critical role in mediating responses of fungi to lignocellulose. The study also shows the presence of different physiological stages in fungal responses which are mostly conserved across different substrates.

Source

Cell therapy for central nervous system disorders: Current obstacles to progress

Cell therapy for central nervous system disorders: Current obstacles to progress

No wonder there is an urgent need for new therapeutic developments having clinical application in treating the disorders associated with the central nervous system. In light of this, various studies are under pipeline which focuses on diseases like Parkinson’s, traumatic brain injury, stroke, and many more. Developments have been carried out where cell therapy using induced pluripotent stem cells (iPS) have been used as a breakthrough. The use of induced pluripotent stem cells for neurorestoration through transplantation has paved a new path in the clinical applications treating neurological disorders. Besides this, iPS cells for long have served as a robust biological system for the development of various therapeutic drugs. Thus, providing deeper insights into the pathological conditions and potential mechanism for its treatment. Even after many recent advances in cell therapies using iPS, the mesenchymal stem cells derived from adult tissues remain one of the popular options as the donor for cell transplantation. In this review article, the breakthrough research made using cell therapy for neurological disorders is discussed along with a detailed understanding of the obstacles in clinical application of therapy and subsequent solutions.

Source