Repurposed anti-cancer epidermal growth factor receptor inhibitors: mechanisms of neuroprotective effects in Alzheimer’s disease

Numerous molecular mechanisms are being examined in an attempt to discover disease-modifying drugs to slow down the underlying neurodegeneration in Alzheimer’s disease.Recent studies have shown the beneficial effects of epidermal growth factor receptor inhibitors on the enhancement of behavioral and pathological sequelae in Alzheimer’s disease.Despite the promising effects of epidermal growth factor receptor inhibitors in Alzheimer’s disease,there is no irrefutable neuroprotective evidence in well-established animal models using epidermal growth factor receptor inhibitors due to many un-explored downstream signaling pathways.This caused controversy about the potential involvement of epidermal growth factor receptor inhibitors in any prospective clinical trial.In this review,the mystery beyond the under-investigation of epidermal growth factor receptor in Alzheimer’s disease will be discussed.Furthermore,their molecular mechanisms in neurodegeneration will be explained.Also,we will shed light on SARS-COVID-19 induced neurological manifestations mediated by epidermal growth factor modulation.Finally,we will discuss future perspectives and under-examined epidermal growth factor receptor downstream signaling pathways that warrant more exploration.We conclude that epidermal growth factor receptor inhibitors are novel effective therapeutic approaches that require further research in attempts to be repositioned in the delay of Alzheimer’s disease progression.

3-to 24-month Follow-up on COVID-19 with Pulmonary Tuberculosis Survivors after Discharge:Results from a Prospective,Multicenter Study

Objective Coronavirus disease 2019(COVID-19)and tuberculosis(TB)are major public health and social issues worldwide.The long-term follow-up of COVID-19 with pulmonary TB(PTB)survivors after discharge is unclear.This study aimed to comprehensively describe clinical outcomes,including sequela and recurrence at 3,12,and 24 months after discharge,among COVID-19 with PTB survivors.Methods From January 22,2020 to May 6,2022,with a follow-up by August 26,2022,a prospective,multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13 hospitals from four provinces in China.Clinical outcomes,including sequela,recurrence of COVID-19,and PTB survivors,were collected via telephone and face-to-face interviews at 3,12,and 24 months after discharge.Results Thirty-two COVID-19 with PTB survivors were included.The median age was 52(45,59)years,and 23(71.9%)were men.Among them,nearly two-thirds(62.5%)of the survivors were moderate,three(9.4%)were severe,and more than half(59.4%)had at least one comorbidity(PTB excluded).The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6%at 3 months to 15.8%at 24 months,with anxiety having a higher proportion over a follow-up.Cough and amnesia recovered at the 12-month follow-up,while anxiety,fatigue,and trouble sleeping remained after 24months.Additionally,one(3.1%)case presented two recurrences of PTB and no re-positive COVID-19during the follow-up period.Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time,while nearly one in six still experience persistent symptoms with a higher proportion of anxiety.The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Necessary problems in re-emergence of COVID-19

The ongoing pandemic of coronavirus disease 2019 poses a great threat to human beings.Although numerous patients have recovered,re-positive cases have been reported in several countries.Till now,we still know very little about the disease and its pathogen severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Therefore,more attention should be paid to the following aspects,such as postdischarge surveillance,asymptomatic infection,re-evaluation of influenza-like symptoms,and dynamic monitoring of genomic mutation of SARS-CoV-2.

Distinct gut microbiota and health outcomes in asymptomatic infection,viral nucleic acid test re-positive,and convalescent COVID-19 cases

Gut microbiota composition is suggested to associate with coronavirus disease 2019(COVID-19)severity,but the impact of gut microbiota on health outcomes is largely unclear.We recruited 81 individuals from Wuhan,China,including 13 asymptomatic infection cases(Group A),24 COVID-19 convalescents with adverse outcomes(Group C),31 severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)re-positive cases(Group D),and 13 non-COVID-19 healthy controls(Group H).The microbial features of Groups A and D were similar and exhibited higher gut microbial diversity and more abundant short-chain fatty acid(SCFA)-producing species than Group C.Group C was enriched with opportunistic pathogens and virulence factors related to adhesion and toxin production.The abundance of SCFA-producing species was negatively correlated,while Escherichia coli was positively correlated with adverse outcomes.All three groups(A,C,and D)were enriched with the mucusdegrading species Akkermansia muciniphila,but decreased with Bacteroides-encoded carbohydrate-active enzymes.The pathways of vitamin B6 metabolic and folate biosynthesis were decreased,while selenocompound metabolism was increased in the three groups.Specifically,the secondary bile acid(BA)metabolic pathway was enriched in Group A.Antibiotic resistance genes were common among the three groups.Conclusively,the gut microbiota was related to the health outcomes of COVID-19.Dietary supplementations(SCFAs,BA,selenium,folate,vitamin B6)may be beneficial to COVID-19 patients.