Mucormycosis: An opportunistic pathogen during COVID-19.

The pandemic of coronavirus disease 2019 (COVID-19) still remains on an upsurge trend. The second wave of this disease has led to panic in many countries, including India and some parts of the world suffering from the third wave. As there are no proper treatment options or remedies available for this deadly infection, supportive care equipment's such as oxygen cylinders, ventilators and heavy use of steroids play a vital role in the management of COVID-19. In the midst of this pandemic, the COVID-19 patients are acquiring secondary infections such as mucormycosis also known as black fungus disease. Mucormycosis is a serious, but rare opportunistic fungal infection that spreads rapidly, and hence prompt diagnosis and treatment are necessary to avoid high rate of mortality and morbidity rates. Mucormycosis is caused by the inhalation of its filamentous (hyphal form) fungi especially in the patients who are immunosuppressed. Recent studies have documented alarming number of COVID-19 patients with mucormycosis infection. Most of these patients had diabetes and were administered steroids for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and were consequently more prone to mucormycosis. Hence, the present review emphasizes mucormycosis and its related conditions, its mechanism in normal and COVID-19 affected individuals, influencing factors and challenges to overcome this black mold infection. Early identification and further investigation of this fungus will significantly reduce the severity of the disease and mortality rate in COVID-19 affected patients.

Mitochondrial dysfunction: A hidden trigger of autism?

Autism is a heterogeneous neurodevelopmental and neuropsychiatric disorder with no precise etiology. Deficits in cognitive functions uncover at early stages and are known to have an environmental and genetic basis. Since autism is multifaceted and also linked with other comorbidities associated with various organs, there is a possibility that there may be a fundamental cellular process responsible for this. These reasons place mitochondria at the point of interest as it is involved in multiple cellular processes predominantly involving metabolism. Mitochondria encoded genes were taken into consideration lately because it is inherited maternally, has its own genome and also functions the time of embryo development. Various researches have linked mitochondrial mishaps like oxidative stress, ROS production and mt-DNA copy number variations to autism. Despite dramatic advances in autism research worldwide, the studies focusing on mitochondrial dysfunction in autism is rather minimal, especially in India. India, owing to its rich diversity, may be able to contribute significantly to autism research. It is vital to urge more studies in this domain as it may help to completely understand the basics of the condition apart from a genetic standpoint. This review focuses on the worldwide and Indian scenario of autism research; mitochondrial abnormalities in autism and possible therapeutic approaches to combat it.

Immunomodulatory effect of mesenchymal stem cells and mesenchymal stem-cell-derived exosomes for COVID-19 treatment.

The world has witnessed unimaginable damage from the coronavirus disease-19 (COVID-19) pandemic. Because the pandemic is growing rapidly, it is important to consider diverse treatment options to effectively treat people worldwide. Since the immune system is at the hub of the infection, it is essential to regulate the dynamic balance in order to prevent the overexaggerated immune responses that subsequently result in multiorgan damage. The use of stem cells as treatment options has gained tremendous momentum in the past decade. The revolutionary measures in science have brought to the world mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exo) as therapeutic opportunities for various diseases. The MSCs and MSCExos have immunomodulatory functions; they can be used as therapy to strike a balance in the immune cells of patients with COVID-19. In this review, we discuss the basics of the cytokine storm in COVID-19, MSCs, and MSC-derived exosomes and the potential and stem-cell-based ongoing clinical trials for COVID-19. [BMB Reports 2020; 53(8): 400-412].

COVID-19: an update on diagnostic and therapeutic approaches.

The unexpected pandemic set off by the novel coronavirus 2019 (COVID-19) has caused severe panic among people worldwide. COVID-19 has created havoc, and scientists and physicians are urged to test the efficiency and safety of drugs used to treat this disease. In such a pandemic situation, various steps have been taken by the government to control and prevent the Severe Acute Respiratory Syndrome coronavirus 2 (SARSCoV- 2). This pandemic situation has forced scientists to rework strategies to combat infectious diseases through drugs, treatment, and control measures. COVID-19 treatment requires both limiting viral multiplication and neutralizing tissue damage induced by an inappropriate immune reaction. Currently, various diagnostic kits to test for COVID-19 are available, and repurposing therapeutics for COVID-19 has shown to be clinically effective. As the global demand for diagnostics and therapeutics continues to rise, it is essential to rapidly develop various algorithms to successfully identify and contain the virus. This review discusses the updates on specimens/samples, recent efficient diagnostics, and therapeutic approaches to control the disease and repurposed drugs mainly focusing on chloroquine/hydroxychloroquine and convalescent plasma (CP). More research is required for further understanding of the influence of diagnostics and therapeutic approaches to develop vaccines and drugs for COVID-19. [BMB Reports 2020; 53(4): 191-205].

COVID-19: A promising cure for the global panic.

The novel Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, which is the causative agent of a potentially fatal disease that is of great global public health concern. The outbreak of COVID-19 is wreaking havoc worldwide due to inadequate risk assessment regarding the urgency of the situation. The COVID-19 pandemic has entered a dangerous new phase. When compared with SARS and MERS, COVID-19 has spread more rapidly, due to increased globalization and adaptation of the virus in every environment. Slowing the spread of the COVID-19 cases will significantly reduce the strain on the healthcare system of the country by limiting the number of people who are severely sick by COVID-19 and need hospital care. Hence, the recent outburst of COVID-19 highlights an urgent need for therapeutics targeting SARS-CoV-2. Here, we have discussed the structure of virus; varying symptoms among COVID-19, SARS, MERS and common flu; the probable mechanism behind the infection and its immune response. Further, the current treatment options, drugs available, ongoing trials and recent diagnostics for COVID-19 have been discussed. We suggest traditional Indian medicinal plants as possible novel therapeutic approaches, exclusively targeting SARS-CoV-2 and its pathways.

Understanding the Role of the Transcription Factor Sp1 in Ovarian Cancer: from Theory to Practice.

Ovarian cancer (OC) is one of the deadliest cancers among women contributing to high risk of mortality, mainly owing to delayed detection. There is no specific biomarker for its detection in early stages. However, recent findings show that over-expression of specificity protein 1 (Sp1) is involved in many OC cases. The ubiquitous transcription of Sp1 apparently mediates the maintenance of normal and cancerous biological processes such as cell growth, differentiation, angiogenesis, apoptosis, cellular reprogramming and tumorigenesis. Sp1 exerts its effects on cellular genes containing putative GC-rich Sp1-binding site in their promoters. A better understanding of the mechanisms underlying Sp1 transcription factor (TF) regulation and functions in OC tumorigenesis could help identify novel prognostic markers, to target cancer stem cells (CSCs) by following cellular reprogramming and enable the development of novel therapies for future generations. In this review, we address the structure, function, and biology of Sp1 in normal and cancer cells, underpinning the involvement of Sp1 in OC tumorigenesis. In addition, we have highlighted the influence of Sp1 TF in cellular reprogramming of iPSCs and how it plays a role in controlling CSCs. This review highlights the drugs targeting Sp1 and their action on cancer cells. In conclusion, we predict that research in this direction will be highly beneficial for OC treatment, and chemotherapeutic drugs targeting Sp1 will emerge as a promising therapy for OC.

Unraveling correlative roles of dopamine transporter (DAT) and Parkin in Parkinson's disease (PD) - A road to discovery?

Parkinson's disease (PD) is a neurodegenerative disorder accompanied by depletion of dopamine(DA) and loss of dopaminergic (DAergic) neurons in the brain that is believed to be responsible for the motor and non-motor symptoms of PD. Dopamine Transporter (DAT) is essential for reuptake of DA into the presynaptic terminal, thereby controlling the availability and spatial activity of released DA. Parkin interacts with proteins involved in the endosomal pathway, suggesting that presynaptic Parkin could regulate the expression of DAT in the plasma membrane. Parkin mutations lead to early synaptic damage and it appears as a crucial gene having a vast functioning area. PD-specific induced pluripotent stem cells (iPSCs) derived DA neurons exist as a potential tool for in-vitro modeling of PD, as they can recapitulate the pathological features of PD. The exact mechanism of PARKIN influenced DAT variations and changes in DA reuptake by DAT remain unknown. Hence, DAT and PARKIN mutated PD-specific iPSCs-derived DA neurons could provide important clues for elucidating the pathogenesis and mechanism of PD. This mysterious and hidden connection may prove to be a boon in disguise, hence, here we review the influence of PARKIN and DAT on DA mechanism and will discuss how these findings underpin the concept of how downregulation or upregulation of DAT is influenced by PARKIN. We conclude that the establishment of new model for PD with a combination of DAT and PARKIN would have a high translational potential, which includes the identification of drug targets and testing of known and novel therapeutic agents.

The potential role of rhythmic entrainment and music therapy intervention for individuals with autism spectrum disorders.

Autism spectrum disorder (ASD) is characterized by social and interpersonal communication disabilities and repetitive motor activities. A deficit in social interaction may be due to motor and synchronization disabilities in individuals with ASD. These disabilities serve as a hindrance for the progression of day-to-day life. ASD individuals are known to have variations in the neural network contributing to changes in their oral-motor activity. As the brain has experience-dependent structural plasticity, these changes in the neural network can probably be reversed with appropriate treatment Music playing a universal role in human life has been studied for its therapeutic potential in rehabilitation of ASD individuals. Music and rhythm have shown a significant potential in improving the oral-motor activities of people affected by ASD. Music based interventions are being used for children diagnosed with ASDs to improve their social communication and motor skills. This article represents the possible role of rhythmic cueing for sensorimotor regulation in ASD individuals. This can serve as a base for further research for the impact of musical therapy on coordination and oral-motor synchronization of individuals diagnosed with ASD.

Stem cell banking: Are South Indian mothers aware?

Umbilical cord blood (UCB) is an important source of stem cells, the heart of regenerative medicine. As the globalization and population of the world continues to increase, we are faced with an inundation of new diseases, affecting millions of people. Research work considering stem cells is essential for developing therapy for various conditions. Reduced availability of UCB serves as a hindrance to promote further research. Hence, India being one of the most densely populated countries in the world, can be considered a potential UCB repository. In this study 428 mothers of children born in the period from 2012 to 2017 were asked to fill questionnaires that evaluated their awareness regarding stem cell banking. This investigation deliberates if expectant mothers in this region are aware of stem cell banking and if there is a significant pattern regarding awareness based on parameters like age, educational qualification, locality, annual income and consulted hospitals. Although, majority of the women were unaware of this facility, knowledge was heightened in wealthy, educated, women from urban areas who consulted private hospitals. Hence, great efforts need to be made to further the awareness of expectant mothers in South India regarding UCB storage and donation.

Ampullary carcinoma-A genetic perspective.

Ampulla of vater carcinoma (AVC) is a rare gastrointestinal tumour that is associated with a high mortality rate and it's often diagnosed at later stages due to lack of clinical symptoms. Early diagnosis of this condition is essential to effectively treat patients for better prognosis. A significant amount of advancement has been made in understanding the molecular nature of cancer in the past decade. A substantial number of mutations and alterations have been detected in various tumors. Despite the occurrence of AVC across the globe, the number of studies conducted on this tumor type remains low; this is largely due to its rare occurrence. Moreover, AVC tissues are complex and contain mutations in oncogenes, tumour suppressors, apoptotic proteins, cell proliferation proteins, cell signaling proteins, transcription factors, chromosomal abnormalities and cellular adhesion proteins. The frequently mutated genes included KRAS, TP53 and SMAD4 and are associated with prognosis. Several molecules of the PI3K, Wnt signaling, TGF-beta pathway and cell cycle have also been altered in AVCs. This review comprises of all the genetic mutations, associated pathways and related prognosis that are involved in AVCs from the year 1989 to 2017. This report can be used as a stepping-stone to establish biomarkers for early diagnosis of AVC and to discover molecular targets for drug therapy.