Medical Hypotheses

Oral Lichen Planus (OLP) is a chronic inflammatory disorder whose exact etiology remains unknown. Inflammatory mediators, cytotoxic CD8+ T cells and mast cells have been hypothesized to mediate the pathogenesis of OLP. COVID-19 pandemic caused by SARS-CoV-2 is marked by cytokine storms in the affected patients. Altered T-cell responses marked by exhaustion of T-cell count with hyperaggressive remaining T-cells and presence of cross-reactive antibodies render infected humans as fertile grounds for development of multisystem disorders...

Zika virus was declared a national emergency by WHO (World Health Organization) in 2016 when its widespread outbreaks and life-threatening complications were reported, especially in newborns and adults. Numerous studies reported that neuroinflammation is one of the significant root-causes behind its major neurological complications like microcephaly and Guillain-Barré syndrome (GBS). In this hypothesis, we propose Transient Receptor Potential Vanilloid 1 channel (TRPV1) as a major culprit in triggering positive inflammatory loop, ultimately leading to sustained neuroinflammation, one of the key clinical findings in Zika induced microcephalic and GBS patients...

Schizophrenia is a severe mental disease involving both neurological and psychiatric abnormalities. Previous studies mainly focus on damage to high-order cognitive dysfunction, which is related to high-level cortical regions such as the prefrontal and temporal lobes. Recent research reveals that impairment of low-level sensory processing occurs in the early stage of schizophrenia, which may be due to impairment of the subcortical magnocellular visual pathway. Moreover, the structure and function of some important nuclei in a subcortical visual pathway are reported to be abnormal in patients with schizophrenia...

Sarcopenia, the age-associated-fragility with loss of skeletal muscle mass and function, often coexists with type 2 diabetes (T2D) in older individuals. Derangement of muscle metabolism and mitochondrial dynamics is critical, particularly in high-energy-demand organs in patients with metabolic disorder. However, targeted therapies to halt or reverse the pathological progression of sarcopenia coexisting with T2D are unavailable. Studies have identified the pathological roles of class I histone deacetylases (HDACs) in both T2D and sarcopenia...

In addition to uncontrolled diabetes and the excess use of corticosteroids, it is believed that other factors may be responsible for the recent spurt of COVID-19 associated mucormycosis (CAM). In the present paper it is argued that COVID-19 increases the susceptibility of the patients to mucormycosis by augmenting the virulence factors of the mucor species, where deficient synthesis of melatonin plays a key role. Melatonin is synthesized from tryptophan via the serotonin pathway and melatonin deficiency in COVID-19 arises from the faulty absorption of tryptophan from the food because SARS-CoV-2 downregulates angiotensin-converting enzyme-2, the chaperone of the transporter of tryptophan...

We hypothesized that neural EGFL like 1 (NELL1) promoter hypermethylation might be associated with the prognosis of gastric cancer. Some studies considered NELL1 as a tumor suppressor gene and our research confirmed for the first time the hypermethylation in the promoter region of NELL1 by the application of mass spectrometry. Promoter hypermethylation can cause the silencing of tumor suppressor genes and promote tumor progression. Based on present studies and research results, we proposed that NELL1 promoter hypermethylation might be associated with cancer staging and the survival of gastric cancer patients and had prognostic value...

No abstract text is available yet for this article.

The adaptive and therapeutic nature of fever has been recognized for centuries and both local and systemic thermotherapy are now used to enhance the effectiveness of both chemotherapy and radiation therapy for cancer. We propose that the success of antiseptic, antibiotic, antipyretic and antimalarial strategies and medications over the past century and a half may have had the unintended effect of releasing precancerous growths and neoplastic foci from the inhibitory effects of intermittent fever. This may be a previously unrecognized factor in the overall rise in cancer rates in the late 19th and early 20th centuries...

Venous thromboembolism (VTE) is a significant public health issue causing severe morbidity and mortality. One of the most vulnerable populations for VTE development are cancer patients. And among them, patients with brain tumors have arguably the highest risk of developing this often fatal complication. Hyperglycemia is a well-known factor which leads to a wide variety of pro-thrombotic changes. In this article, we review the current literature on the topic of VTE in brain tumor patients. We also discuss the known correlation between VTE and glycemia, as well as the importance and frequency of glycemia dysregulation in brain tumor patients...

As bacteriophage therapy is being investigated more as an alternative to antibiotics, laboratories are isolating and characterizing the functions of bacteriophages. Additionally, with large variations between gut microbiome studies and inconsistencies in results, there is a need for discrete characterization of specific gut microbes in situ. This hypothesis paper describes a method to utilize bacteriophages in order to outline the functions of specific gut bacteria in existing biological systems with minimal disturbance...

The COVID-19 pandemic has been characterised by successiveoutbreaks effecting large swathes of the world's populations. These waves of infection have been mainly driven by a number of more transmissiblevariants which appear to evade the populations' immunity gained from previous outbreaks. There appears to be a link between COVID-19 and a ubiquitous airborne pollutant calledparticulate matter, PM2.5. Particulate matter through a number of mechanisms, including its anthropogenic effect, appears to be associated with the incidence and the mortality related to the COVID-19 pandemic...

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer with high rates of tumor relapse and metastasis. The existing drugs for treatment of TNBC are unable to target the cells of origin (breast cancer stem cells) of TNBC. TNF-α related apoptosis inducing ligand (TRAIL) has propensity to target TNBC cells including cancer stem cells. However, resistance to TRAIL due to activation of anti-apoptotic mechanisms is a limitation for TRAIL based anticancer therapy for TNBC. In the present study we propose an hypothesis for effective targeting of triple negative breast cancer by overcoming TRAIL resistance...

No abstract text is available yet for this article.

SARS-COV-2 infection causes severe respiratory tract illness leading to asphyxia and death. The onset of infection is associated with loss of smell, blurred vision, headache with bronchopulmonary symptoms. The clinical observations of neurological abnormalities lead us to address the question, does the virus enter into brain and what is the underlying mechanism of brain infection? The working hypothesis is, SARS-COV-2 Spike epitopes modify blood brain barrier and infect glial cells to induce brain inflammation in genetically diverse human population...

A subset of COVID-19 patients is experiencing secondary immune thrombocytopenia, also called immune thrombocytopenic purpura (ITP) or secondary hemophagocytic lymphohistiocytosis (HLH). The pathogenesis of SARS-CoV-2 associated thrombocytopenia is unknown. Very rare cases of vaccine induced prothrombotic immune thrombocytopenia (VIPIT) are occurring associated with COVID-19 vaccines. COVID-19 VIPIT is associated with autoantibodies targeting platelet factor 4 (PF4) for COVID-19 adenovirus vaccines. Herein, four models for hemophagocytic histocytes contributions to the etiology of thrombocytopenia associated with SARS-CoV-2 are proposed...

No abstract text is available yet for this article.

Sedentary lifestyle increases the risk of hospitalization for COVID-19 independently of other factors. There is enough statistics to show that exercise prevents severe forms of COVID-19, but current recommendations do not set an upper limit for exercise intensity. The hypothesis presented in the paper states that intense exercise, through blood hypoxia, increases the expression of transmembrane angiotensin-converting enzyme 2 (tACE2) in the vascular endothelium, increasing the risk of developing serious forms of disease, especially in the untrained...

The body's innate and acquiredimmunesystems are critical in responses to a wide spectrum of assaults, including SARS-CoV-2 infection. We identify studies of autoimmunity to support our hypothesis that a high intelligence quotient (IQ) may put children at increased risk for severe COVID-19 sequelae; especially those whose viral load is high and/or who develop multisystem inflammatory syndrome in children (MIS-C). MIS-C is associated with a higher risk of COVID-19 morbidity and death, even in otherwise healthy children...

Alpha-casozepine (α CZP), a tryptic hydrolysate of milk casein is a decapeptide shown to promote sleep and produce anxiolytic or anticonvulsant activity. Intriguingly, studies indicate structural similarities to benzodiazepine (BZD)-like molecules (e.g., diazepam), resulting in positive modulation of γ-aminobutyric acid A type (GABAA ) receptors. However, some unexplained anomalous behaviour of α-CZP includes 1) 1000 times less affinity for BZD site on GABAA receptor in vitro conditions, whereas in vivo it showed 10-fold increased affinity when compared to diazepam; 2) anxiolytic effects were observed only in stressed conditions and 3) unlike diazepam, it failed to exhibit dependence or habituation...

Corneal disease remains to be one of the leading causes of blindness in the world and limbal stem cell (LSC) therapy is a promising therapy for LSC deficiency, which is associated with the diseased corneal epithelium repair. Soft substrate could effectively promote the stemness maintenance of LSC and thus modification of cell culture substrate would help in the potential LSC deficiency therapy. Both Hippo-Yes-associated protein (YAP) and Notch pathway have been reported to affect the LSC function, however, the detailed mechanisms remain unclear...