-
Viruses May 2024The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple... (Review)
Review
The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple SARS-CoV-2 variants were reported globally, and a wide range of symptoms existed. Individuals who contract COVID-19 continue to suffer for a long time, known as long COVID or post-acute sequelae of COVID-19 (PASC). While COVID-19 vaccines were widely deployed, both unvaccinated and vaccinated individuals experienced long-term complications. To date, there are no treatments to eradicate long COVID. We recently conceived a new approach to treat COVID in which a 15-amino-acid synthetic peptide (SPIKENET, SPK) is targeted to the ACE2 receptor binding domain of SARS-CoV-2, which prevents the virus from attaching to the host. We also found that SPK precludes the binding of spike glycoproteins with the receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) of a coronavirus, murine hepatitis virus-1 (MHV-1), and with all SARS-CoV-2 variants. Further, SPK reversed the development of severe inflammation, oxidative stress, tissue edema, and animal death post-MHV-1 infection in mice. SPK also protects against multiple organ damage in acute and long-term post-MHV-1 infection. Our findings collectively suggest a potential therapeutic benefit of SPK for treating COVID-19.
Topics: SARS-CoV-2; Humans; COVID-19; Animals; Spike Glycoprotein, Coronavirus; Mice; Post-Acute COVID-19 Syndrome; Angiotensin-Converting Enzyme 2; Peptides; Antiviral Agents; COVID-19 Drug Treatment
PubMed: 38932130
DOI: 10.3390/v16060838 -
Viruses May 2024The COVID-19 pandemic, which emerged in early 2020, has had a profound and lasting impact on global health, resulting in over 7.0 million deaths and persistent...
The COVID-19 pandemic, which emerged in early 2020, has had a profound and lasting impact on global health, resulting in over 7.0 million deaths and persistent challenges. In addition to acute concerns, there is growing attention being given to the long COVID health consequences for survivors of COVID-19 with documented cases of cardiovascular abnormalities, liver disturbances, lung complications, kidney issues, and noticeable cognitive deficits. Recent studies have investigated the physiological changes in various organs following prolonged exposure to murine hepatitis virus-1 (MHV-1), a coronavirus, in mouse models. One significant finding relates to the effects on the gastrointestinal tract, an area previously understudied regarding the long-lasting effects of COVID-19. This research sheds light on important observations in the intestines during both the acute and the prolonged phases following MHV-1 infection, which parallel specific changes seen in humans after exposure to SARS-CoV-2. Our study investigates the histopathological alterations in the small intestine following MHV-1 infection in murine models, revealing significant changes reminiscent of inflammatory bowel disease (IBD), celiac disease. Notable findings include mucosal inflammation, lymphoid hyperplasia, goblet cell hyperplasia, and immune cell infiltration, mirroring pathological features observed in IBD. Additionally, MHV-1 infection induces villous atrophy, altered epithelial integrity, and inflammatory responses akin to celiac disease and IBD. SPIKENET (SPK) treatment effectively mitigates intestinal damage caused by MHV-1 infection, restoring tissue architecture and ameliorating inflammatory responses. Furthermore, investigation into long COVID reveals intricate inflammatory profiles, highlighting the potential of SPK to modulate intestinal responses and restore tissue homeostasis. Understanding these histopathological alterations provides valuable insights into the pathogenesis of COVID-induced gastrointestinal complications and informs the development of targeted therapeutic strategies.
Topics: Animals; Mice; COVID-19; Disease Models, Animal; Murine hepatitis virus; SARS-CoV-2; Intestinal Mucosa; Intestines; Intestine, Small; Female
PubMed: 38932125
DOI: 10.3390/v16060832 -
Nutrients Jun 2024Branched-chain amino acids (BCAAs), as essential amino acids, engage in various physiological processes, such as protein synthesis, energy supply, and cellular... (Review)
Review
Branched-chain amino acids (BCAAs), as essential amino acids, engage in various physiological processes, such as protein synthesis, energy supply, and cellular signaling. The liver is a crucial site for BCAA metabolism, linking the changes in BCAA homeostasis with the pathogenesis of a variety of liver diseases and their complications. Peripheral circulating BCAA levels show complex trends in different liver diseases. This review delineates the alterations of BCAAs in conditions including non-alcoholic fatty liver disease, hepatocellular carcinoma, cirrhosis, hepatic encephalopathy, hepatitis C virus infection, and acute liver failure, as well as the potential mechanisms underlying these changes. A significant amount of clinical research has utilized BCAA supplements in the treatment of patients with cirrhosis and liver cancer. However, the efficacy of BCAA supplementation in clinical practice remains uncertain and controversial due to the heterogeneity of studies. This review delves into the complicated relationship between BCAAs and liver diseases and tries to untangle what role BCAAs play in the occurrence, development, and outcomes of liver diseases.
Topics: Humans; Amino Acids, Branched-Chain; Liver Diseases; Dietary Supplements; Liver; Liver Cirrhosis; Liver Neoplasms; Carcinoma, Hepatocellular; Non-alcoholic Fatty Liver Disease; Hepatic Encephalopathy
PubMed: 38931228
DOI: 10.3390/nu16121875 -
Medicina (Kaunas, Lithuania) Jun 2024Hepatitis E virus (HEV) infection is typically a self-limiting, acute illness that spreads through the gastrointestinal tract but replicates in the liver. However,... (Review)
Review
Hepatitis E virus (HEV) infection is typically a self-limiting, acute illness that spreads through the gastrointestinal tract but replicates in the liver. However, chronic infections are possible in immunocompromised individuals. The HEV virion has two shapes: exosome-like membrane-associated quasi-enveloped virions (eHEV) found in circulating blood or in the supernatant of infected cell cultures and non-enveloped virions ("naked") found in infected hosts' feces and bile to mediate inter-host transmission. Although HEV is mainly spread via enteric routes, it is unclear how it penetrates the gut wall to reach the portal bloodstream. Both virion types are infectious, but they infect cells in different ways. To develop personalized treatment/prevention strategies and reduce HEV impact on public health, it is necessary to decipher the entry mechanism for both virion types using robust cell culture and animal models. The contemporary knowledge of the cell entry mechanism for these two HEV virions as possible therapeutic target candidates is summarized in this narrative review.
Topics: Humans; Hepatitis E virus; Hepatitis E; Virion; Animals
PubMed: 38929615
DOI: 10.3390/medicina60060998 -
Communicable Diseases Intelligence... Jun 2024Hepatitis B vaccination was nationally funded for adolescents in 1996, with inclusion of universal infant immunisation under the National Immunisation Program (NIP) in...
INTRODUCTION
Hepatitis B vaccination was nationally funded for adolescents in 1996, with inclusion of universal infant immunisation under the National Immunisation Program (NIP) in May 2000. This study describes hepatitis B epidemiology in Australia in the two decades since 2000.
METHODS
This article analyses newly-acquired (within the prior 24 months) and unspecified (all other) hepatitis B notifications (2000-2019) from the National Notifiable Diseases Surveillance System; acute hepatitis B hospitalisations (2001-2019) from the National Hospital Morbidity Database; and acute (2000-2019) and chronic (2006-2019) hepatitis B deaths from the Australian Bureau of Statistics and Australian Coordinating Registry. Rates over the reporting period were described overall, and by age group, sex, and Aboriginal and Torres Strait Islander status (Aboriginal and/or Torres Strait Islander versus other [neither Aboriginal nor Torres Strait Islander, unknown or not stated]). Trend analyses were performed using Poisson or negative binomial regression. Additional analyses were performed for the cohort born after May 2000.
RESULTS AND DISCUSSION
The annual all-age notification rate per 100,000 per year declined (p < 0.001) from 2.13 in 2000 to 0.65 in 2019 for newly-acquired hepatitis B and from 38.3 to 22.3 for unspecified hepatitis B (likely to predominantly represent chronic hepatitis B). Newly-acquired and unspecified hepatitis B notification rates were lowest among children aged < 15 years. The most substantial reductions in notification rates of newly-acquired hepatitis B were among adolescents aged 15-19 years and young adults aged 20-24 and 25-29 years (respectively 17-, 11-, and 7-fold); these age groups also recorded the most substantial reductions in unspecified hepatitis B notifications (respectively 5-, 3.5-, and 2-fold). Newly-acquired hepatitis B notification and acute hepatitis B mortality rates were two- to threefold higher in males than females. The all-age newly-acquired hepatitis B notification rate in Aboriginal and Torres Strait Islander people decreased twofold between 2000 and 2019, but remained threefold higher than in other people. Acute hepatitis B hospitalisations also declined over the study period (p < 0.001) and followed similar patterns. There were no acute or chronic hepatitis B deaths among people born after May 2000; this cohort featured 52 newly-acquired and 887 unspecified hepatitis B notifications. Due to lack of data on country of birth (and hence eligibility for infant vaccination under the NIP or overseas programs), vaccination status and likely transmission routes, we were unable to assess factors contributing to these potentially preventable infections.
CONCLUSION
Adolescent and infant immunisation under the NIP has led to significant reductions in notification rates of newly-acquired hepatitis B, and in acute hepatitis B hospitalisation rates, both overall and in Aboriginal and Torres Strait Islander people. Unspecified hepatitis B notification rates have also greatly decreased in children and young adults, likely largely due to the impact of overseas infant immunisation programs on prevalence in child and adolescent migrants. Work to improve completeness of variables within national datasets is crucial, along with enhanced surveillance of both newly-acquired and unspecified hepatitis B cases to investigate transmission routes, vaccination status and factors contributing to acquisition of hepatitis B, in order to optimise the impact of immunisation programs and ensure linkage with care.
Topics: Humans; Australia; Adolescent; Hepatitis B; Adult; Female; Male; Young Adult; Child; Hepatitis B Vaccines; Child, Preschool; Infant; Middle Aged; Native Hawaiian or Other Pacific Islander; Aged; Immunization Programs; Infant, Newborn; Vaccination; Disease Notification; Hospitalization
PubMed: 38926652
DOI: 10.33321/cdi.2024.48.44 -
Life Sciences Jun 2024Lung cancer is among leading causes of death worldwide. The five-year survival rate of this disease is extremely low (17.8 %), mainly due to difficult early diagnosis...
Lung cancer is among leading causes of death worldwide. The five-year survival rate of this disease is extremely low (17.8 %), mainly due to difficult early diagnosis and to the limited efficacy of currently available chemotherapeutics. This underlines the necessity to develop innovative therapies for lung cancer. In this context, drug repurposing represents a viable approach, as it reduces the turnaround time of drug development removing costs associated to safety testing of new molecular entities. Ribavirin, an antiviral molecule used to treat hepatitis C virus infections, is particularly promising as repurposed drug for cancer treatment, having shown therapeutic activity against glioblastoma, acute myeloid leukemia, and nasopharyngeal carcinoma. In the present study, we thoroughly investigated the in vitro anticancer activity of ribavirin against A549 human lung adenocarcinoma cells. From a functional standpoint, ribavirin significantly inhibits cancer hallmarks such as cell proliferation, migration, and colony formation. Mechanistically, ribavirin downregulates the expression of numerous proteins and genes regulating cell migration, proliferation, apoptosis, and cancer angiogenesis. The anticancer potential of ribavirin was further investigated in silico through gene ontology pathway enrichment and protein-protein interaction networks, identifying five putative molecular interactors of ribavirin (Erb-B2 Receptor Tyrosine Kinase 4 (Erb-B4); KRAS; Intercellular Adhesion Molecule 1 (ICAM-1); amphiregulin (AREG); and neuregulin-1 (NRG1)). These interactions were characterized via molecular docking and molecular dynamic simulations. The results of this study highlight the potential of ribavirin as a repurposed chemotherapy against lung cancer, warranting further studies to ascertain the in vivo anticancer activity of this molecule.
PubMed: 38925223
DOI: 10.1016/j.lfs.2024.122859 -
Journal of Neurovirology Jun 2024The cellular prion protein (PrP) is an extracellular cell membrane protein. Due to its diversified roles, a definite role of PrP has been difficult to establish. During...
The cellular prion protein (PrP) is an extracellular cell membrane protein. Due to its diversified roles, a definite role of PrP has been difficult to establish. During viral infection, PrP has been reported to play a pleiotropic role. Here, we have attempted to envision the function of PrP in the neurotropic m-CoV-MHV-RSA59-induced model of neuroinflammation in C57BL/6 mice. A significant upregulation of PrP at protein and mRNA levels was evident in infected mouse brains during the acute phase of neuroinflammation. Furthermore, investigation of the effect of MHV-RSA59 infection on PrP expression in specific neuronal, microglial, and astrocytoma cell lines, revealed a differential expression of prion protein during neuroinflammation. Additionally, siRNA-mediated downregulation of prnp transcripts reduced the expression of viral antigen and viral infectivity in these cell lines. Cumulatively, our results suggest that PrP expression significantly increases during acute MHV-RSA59 infection and that PrP also assists in viral infectivity and viral replication.
PubMed: 38922550
DOI: 10.1007/s13365-024-01215-w -
Emerging Microbes & Infections Jun 2024Background Hepatitis E virus (HEV) is an important cause of acute hepatitis, however, is highly neglected and largely underreported. This study aimed to describe the...
Background Hepatitis E virus (HEV) is an important cause of acute hepatitis, however, is highly neglected and largely underreported. This study aimed to describe the detailed epidemiology of hepatitis E (HE) through a 10-year surveillance. A community-based active hepatitis surveillance was conducted between November 2007 and October 2017 in 11 townships of Dongtai City in China, involving 355,673 residents. Serum samples were obtained from patients presenting with hepatitis symptoms for more than 3 days. Serum alanine aminotransferase (ALT) levels greater than 2.5 times the upper limit of normal (ULN) were considered acute hepatitis. Samples were subsequently tested for IgG and IgM anti-HEV antibodies, HEV RNA, and hepatitis B surface antigen (HBsAg). The data indicated the incidence of HE fluctuated downward from 2007 to 2017, with an average annual age-standardized incidence of 17.50 per 100,000, exceeding the 10.26 per 100,000 in the National Notifiable Disease Report System (NNDRS). The incidence was notably higher among males (20.95 per 100,000) and individuals aged 50-69 years (37.47 per 100,000). Genotype 4 (HEV-4) was the predominantly circulating genotype during the study period. Furthermore, the study revealed the incidence of hepatitis with HEV and hepatitis B virus (HBV) co-infection was 4.99 per 100,000. Conclusion The active surveillance system identified a higher incidence of HE compared to NNDRS, with a decreased prevalence over a 10-year period. While efforts are still needed to prevent HE in high-risk populations, including individuals with hepatitis B and the elderly.
PubMed: 38922438
DOI: 10.1080/22221751.2024.2373315 -
Critical Care Explorations Jul 2024COVID-19 may injure the kidney tubules via activation of inflammatory host responses and/or direct viral infiltration. Most studies of kidney injury in COVID-19 lacked...
IMPORTANCE
COVID-19 may injure the kidney tubules via activation of inflammatory host responses and/or direct viral infiltration. Most studies of kidney injury in COVID-19 lacked contemporaneous controls or measured kidney biomarkers at a single time point.
OBJECTIVES
To better understand mechanisms of acute kidney injury in COVID-19, we compared kidney outcomes and trajectories of tubular injury, viability, and function in prospectively enrolled critically ill adults with and without COVID-19.
DESIGN, SETTING, AND PARTICIPANTS
The COVID-19 Host Response and Outcomes study prospectively enrolled patients admitted to ICUs in Washington State with symptoms of lower respiratory tract infection, determining COVID-19 status by nucleic acid amplification on arrival.
MAIN OUTCOMES AND MEASURES
We evaluated major adverse kidney events (MAKE) defined as a doubling of serum creatinine, kidney replacement therapy, or death, in 330 patients after inverse probability weighting. In the 181 patients with available biosamples, we determined trajectories of urine kidney injury molecule-1 (KIM-1) and epithelial growth factor (EGF), and urine:plasma ratios of endogenous markers of tubular secretory clearance.
RESULTS
At ICU admission, the mean age was 55 ± 16 years; 45% required mechanical ventilation; and the mean serum creatinine concentration was 1.1 mg/dL. COVID-19 was associated with a 70% greater occurrence of MAKE (relative risk 1.70; 95% CI, 1.05-2.74) and a 741% greater occurrence of KRT (relative risk 7.41; 95% CI, 1.69-32.41). The biomarker cohort had a median of three follow-up measurements. Urine EGF, secretory clearance ratios, and estimated glomerular filtration rate (eGFR) increased over time in the COVID-19 negative group but remained unchanged in the COVID-19 positive group. In contrast, urine KIM-1 concentrations did not significantly change over the course of the study in either group.
CONCLUSIONS
Among critically ill adults, COVID-19 is associated with a more protracted course of proximal tubular dysfunction and reduced eGFR despite similar degrees of kidney injury.
Topics: Humans; COVID-19; Middle Aged; Critical Illness; Male; Acute Kidney Injury; Female; Prospective Studies; Aged; Hepatitis A Virus Cellular Receptor 1; SARS-CoV-2; Adult; Biomarkers; Kidney Tubules; Creatinine; Intensive Care Units; Washington; Epidermal Growth Factor; Renal Replacement Therapy
PubMed: 38922318
DOI: 10.1097/CCE.0000000000001109 -
Medical Review (2021) Jun 2024A major worldwide health concern, chronic hepatitis B necessitates precise prognostic and diagnostic indicators for clinical guidance. This article highlights the... (Review)
Review
A major worldwide health concern, chronic hepatitis B necessitates precise prognostic and diagnostic indicators for clinical guidance. This article highlights the clinical importance and current issues of the major markers used in both the detection and prognosis of chronic hepatitis B. An important indicator of an ongoing and persistent infection is the hepatitis B surface antigen. Hepatitis B virus DNA quantification monitoring aids in assessing viral load and hepatic cancer risk. While limited evidence of liver damage is provided by alanine aminotransferase levels, the hepatitis B core antibody verifies acute infection. Seroconversion to the hepatitis B e antibody is linked to a lower risk of disease development, and the hepatitis B e antigen status is a critical prognostic factor. Treatment choices are guided by a biopsy of the liver or minimally invasive liver fibrosis detection. Genotypes of the hepatitis B virus and host variables influence the prognosis by adding to the disease's variability. Noninvasive techniques to evaluate the severity of the disease are provided by serum markers of fibrosis, such as the fibrosis score based on four criteria and the aspartate aminotransferase-to-platelet ratio index. The requirement for indicators that distinguish between distinct viral phases and increase specificity in evaluating liver damage is one of the challenges facing chronic hepatitis B research. Even though it is quite difficult to find reliable biomarkers for resistance especially when it comes to hepatocellular cancer risk estimation, there are advanced methods, which include imaging and omics that can help in improving the accuracy of the diagnostics and prognosis. Interventions early point that improve patient outcomes are made possible using diagnostics and prognostics as they are quite effective in managing the complicated landscape of chronic hepatitis B. Key in addressing these challenges today and improving the diagnostic and prognostic markers in the future, particularly those that would support the development of successful treatment plans for people living with chronic hepatitis B virus (HBV), are scientific research, technological advances and collaborations.
PubMed: 38919396
DOI: 10.1515/mr-2024-0022