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Journal of Leukocyte Biology May 2024Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive impairment. β-amyloid (Aβ) is one of the typical pathological...
Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive impairment. β-amyloid (Aβ) is one of the typical pathological features of AD, and its accumulation leads to neuronal death from oxidative stress. Here, we found that hederagenin (HG), a natural product, exhibits anti-tumor, anti-inflammatory, anti-depressant, anti-neurodegenerative biological activities. However, whether HG has anti-Aβ activity remains unclear. Based on the characteristics of HG, it is hypothesized that HG has biological activity against Aβ injury. Therefore, Aβ-injured SH-SY5Y cells were constructed, and the protective effect of HG against Aβ injury was further evaluated using C. elegans. The results showed that HG increased superoxide dismutase activity, effectively reduced Aβ-induced oxidative damage, and reduced apoptosis via the PI3 K/Akt signaling pathway. HG inhibited Aβ deposition and delayed senescence and paralysis in the C. elegans strain, CL4176. HG showed inhibitory effects on Aβ; therefore, more natural active products are expected to be applied in AD therapy.
PubMed: 38814954
DOI: 10.1093/jleuko/qiae124 -
AIDS (London, England) Jul 2024
Topics: Humans; HIV Infections; COVID-19 Vaccines; COVID-19; SARS-CoV-2; mRNA Vaccines; Vaccines, Synthetic; Antibodies, Viral
PubMed: 38814720
DOI: 10.1097/01.aids.0001010204.00856.15 -
Turkish Journal of Medical Sciences 2023To determine the knowledge about and acceptance level of monkeypox vaccine in men who have sex with men (MSM).
BACKGROUND/AIM
To determine the knowledge about and acceptance level of monkeypox vaccine in men who have sex with men (MSM).
MATERIALS AND METHODS
A 14-item questionnaire, developed by the European Centers for Disease Control (ECDC), was presented online to MSM, aged ≥18 years old, via smartphone applications (Grindr and Hornet), between June 30th and August 12th, 2022.
RESULTS
Of the 737 participants who completed the survey, 678 were born in Türkiye and 59 were migrants/visitors born in different countries. All of the participants were living in Türkiye. The median age was 31 (range 18-68) years. Overall, 21.9% were HIV-positive, 94.9% were using antiretroviral therapy (ART), 3.9% reported using preexposure prophylaxis (PrEP), 9.9% had been diagnosed with a sexually transmitted infection (STI) in the past 12 months, and 10.1% reported using chemicals during sexual intercourse in the past three months.Participants aged 45-54 were significantly more concerned about being treated differently due to monkeypox than those in the other age groups (p = 0.038). Compared to the participants who were HIV-negative, those who were HIV-positive were significantly more worried about acquiring monkeypox (34.1% were very worried and 43.6% were worried, p = 0.033), were more likely to definitely or probably get vaccinated if offered (67.6% and 80.6%, respectively, p = 0.002), and were more concerned about being exposed to different attitudes due to monkeypox (37.0% and 53.3%, respectively, p < 0.01). Among those using ART, 82.3% and 50.0% reported that they would definitely or probably get vaccinated if offered, respectively (p = 0.046). There were no significant differences between groups for the remaining parameters.
CONCLUSION
Despite the low level of knowledge about monkeypox, the majority of the participants reported that they believed in the vaccine's efficacy. Those who were HIV-positive were particularly more concerned about monkeypox and were more willing to protect themselves compared to those who were HIV-negative.
Topics: Humans; Male; Adult; Middle Aged; Homosexuality, Male; Health Knowledge, Attitudes, Practice; Young Adult; Aged; Surveys and Questionnaires; Adolescent; Patient Acceptance of Health Care; Mpox (monkeypox); Turkey; HIV Infections
PubMed: 38813016
DOI: 10.55730/1300-0144.5679 -
Scientific Reports May 2024In order to become bioactive, proteins must be translated and protected from aggregation during biosynthesis. The ribosome and molecular chaperones play a key role in...
In order to become bioactive, proteins must be translated and protected from aggregation during biosynthesis. The ribosome and molecular chaperones play a key role in this process. Ribosome-bound nascent chains (RNCs) of intrinsically disordered proteins and RNCs bearing a signal/arrest sequence are known to interact with ribosomal proteins. However, in the case of RNCs bearing foldable protein sequences, not much information is available on these interactions. Here, via a combination of chemical crosslinking and time-resolved fluorescence-anisotropy, we find that nascent chains of the foldable globin apoHmp interact with ribosomal protein L23 and have a freely-tumbling non-interacting N-terminal compact region comprising 63-94 residues. Longer RNCs (apoHmp) also interact with an additional yet unidentified ribosomal protein, as well as with chaperones. Surprisingly, the apparent strength of RNC/r-protein interactions does not depend on nascent-chain sequence. Overall, foldable nascent chains establish and expand interactions with selected ribosomal proteins and chaperones, as they get longer. These data are significant because they reveal the interplay between independent conformational sampling and nascent-protein interactions with the ribosomal surface.
Topics: Ribosomes; Ribosomal Proteins; Protein Folding; Protein Binding; Molecular Chaperones; Intrinsically Disordered Proteins; Protein Biosynthesis; Models, Molecular; Protein Conformation; Humans
PubMed: 38811604
DOI: 10.1038/s41598-024-61274-1 -
Science Advances May 2024Viruses, bacteria, and parasites frequently cause infections in the gastrointestinal tract, but traditional vaccination strategies typically elicit little or no mucosal...
Viruses, bacteria, and parasites frequently cause infections in the gastrointestinal tract, but traditional vaccination strategies typically elicit little or no mucosal antibody responses. Here, we report a strategy to effectively concentrate immunogens and adjuvants in gut-draining lymph nodes (LNs) to induce gut-associated mucosal immunity. We prepared nanoemulsions (NEs) based on biodegradable oils commonly used as vaccine adjuvants, which encapsulated a potent Toll-like receptor agonist and displayed antigen conjugated to their surface. Following intraperitoneal administration, these NEs accumulated in gut-draining mesenteric LNs, priming strong germinal center responses and promoting B cell class switching to immunoglobulin A (IgA). Optimized NEs elicited 10- to 1000-fold higher antigen-specific IgG and IgA titers in the serum and feces, respectively, compared to free antigen mixed with NE, and strong neutralizing antibody titers against severe acute respiratory syndrome coronavirus 2. Thus, robust gut humoral immunity can be elicited by exploiting the unique lymphatic collection pathways of the gut with a lymph-targeting vaccine formulation.
Topics: Animals; Immunity, Humoral; Mice; Gastrointestinal Tract; Lymphoid Tissue; Immunity, Mucosal; SARS-CoV-2; COVID-19; Antibodies, Viral; Lymph Nodes; Immunoglobulin A; COVID-19 Vaccines; Antibodies, Neutralizing; Female; B-Lymphocytes; Adjuvants, Vaccine; Mice, Inbred C57BL; Humans
PubMed: 38809992
DOI: 10.1126/sciadv.adn7786 -
Global Health, Science and Practice Jun 2024There is limited evidence on COVID-19 vaccination uptake among people living with HIV (PLHIV) and health care workers (HCWs), with the current evidence concentrated in...
BACKGROUND
There is limited evidence on COVID-19 vaccination uptake among people living with HIV (PLHIV) and health care workers (HCWs), with the current evidence concentrated in high-income countries. There is also limited documentation in the published literature regarding the feasibility and lessons from implementing targeted vaccination strategies to reach PLHIV and HCWs in low- and middle-income countries.
PROGRAM DEVELOPMENT, PILOTING, AND IMPLEMENTATION
We designed and implemented multifaceted strategies to scale up targeted COVID-19 vaccination among PLHIV and HCWs in 11 administrative regions on the mainland of Tanzania plus Zanzibar. An initial 6-week intensification strategy was implemented using a diverse partnership model comprising key stakeholders at the national- and subnational levels. A layered package of strategies included expanding the number of certified vaccinators, creating vaccination points within HIV clinics, engaging HCWs to address their concerns, and building the capacity of HCWs as "champions" to promote and facilitate vaccination. We then closely monitored COVID-19 vaccination uptake in 562 high-volume HIV clinics. Between September 2021 and September 2022, the proportion of fully vaccinated adult PLHIV increased from <1% to 97% and fully vaccinated HCWs increased from 23% to 80%.
LESSONS AND IMPLICATIONS
Our intra-action review highlighted the importance of leveraging a strong foundation of existing partnerships and platforms, integrating COVID-19 vaccination points within HIV clinics, and refining strategies to increase vaccination demand while ensuring continuity of vaccine supply to meet the increased demand. Lessons from Tanzania can inform targeted vaccination of vulnerable groups in future health emergencies.
Topics: Humans; Tanzania; HIV Infections; Health Personnel; COVID-19; COVID-19 Vaccines; SARS-CoV-2; Vaccination
PubMed: 38806223
DOI: 10.9745/GHSP-D-23-00281 -
Nature Communications May 2024Avian influenza A virus H7N9 causes severe human infections with >30% fatality. Currently, there is no H7N9-specific prevention or treatment for humans. Here, from a...
Avian influenza A virus H7N9 causes severe human infections with >30% fatality. Currently, there is no H7N9-specific prevention or treatment for humans. Here, from a 2013 H7N9 convalescent case in Hong Kong, we isolate four hemagglutinin (HA)-reactive monoclonal antibodies (mAbs), with three directed to the globular head domain (HA1) and one to the stalk domain (HA2). Two clonally related HA1-directed mAbs, H7.HK1 and H7.HK2, potently neutralize H7N9 and protect female mice from lethal H7N9/AH1 challenge. Cryo-EM structures reveal that H7.HK1 and H7.HK2 bind to a β14-centered surface and disrupt the 220-loop that makes hydrophobic contacts with sialic acid on an adjacent protomer, thereby blocking viral entry. Sequence analysis indicates the lateral patch targeted by H7.HK1 and H7.HK2 to be conserved among influenza subtypes. Both H7.HK1 and H7.HK2 retain HA1 binding and neutralization capacity to later H7N9 isolates from 2016-2017, consistent with structural data showing that the antigenic mutations during this timeframe occur at their epitope peripheries. The HA2-directed mAb H7.HK4 lacks neutralizing activity but when used in combination with H7.HK2 moderately augments female mouse protection. Overall, our data reveal antibodies to a conserved lateral HA1 supersite that confer neutralization, and when combined with a HA2-directed non-neutralizing mAb, augment protection.
Topics: Influenza A Virus, H7N9 Subtype; Animals; Antibodies, Neutralizing; Humans; Hemagglutinin Glycoproteins, Influenza Virus; Female; Influenza, Human; Mice; Antibodies, Viral; Antibodies, Monoclonal; Mice, Inbred BALB C; Cryoelectron Microscopy; Orthomyxoviridae Infections; Epitopes
PubMed: 38802413
DOI: 10.1038/s41467-024-48758-4 -
Protein & Cell May 2024
PubMed: 38801319
DOI: 10.1093/procel/pwae033 -
Annali Di Igiene : Medicina Preventiva... May 2024Up until recently, monkeypox (mpox) was considered to be a rare zoonotic infection restricted to Central and West Africa. However, in July 2022, the World Health...
BACKGROUND
Up until recently, monkeypox (mpox) was considered to be a rare zoonotic infection restricted to Central and West Africa. However, in July 2022, the World Health Organization declared mpox to be a public health emergency of international concern, after there were several outbreaks in non-endemic countries. This study assessed the information channels used by individuals accessing the "Telefono Verde AIDS e Infezioni Sessualmente Trasmesse" of Istituto Superiore di Sanità (National Institute of Health in Italy) with regard to mpox. We also evaluated their awareness, and knowledge about mpox focusing on transmission and prevention.
METHODS
This is a cross-sectional study conducted on "Telefono Verde AIDS e Infezioni Sessualmente Trasmesse" users, between January and April 2023. The target population was helpline users who were older than 18 years of age, and were phoning the service for the first time (i.e. who have not phoned in the last 12 months). Participants were interviewed using a questionnaire containing 19 questions filled by the interviewer. Collected data were analysed through descriptive statistics, and significance testing.
RESULTS
From January to April 2023, "Telefono Verde AIDS e Infezioni Sessualmente Trasmesse" received 2,389 phone calls, 216 of which participated in this study. Most of these were male (85.2%; n=186), single (79.2%; n=171) and in employment (72.2%; n=156). Awareness about mpox was high (71.3%; n=154), with the central and south/islands regional areas having the highest percentage of participants who heard about the virus (84.3%; n=43 vs 72.4%; n=42; p=0.078). Television was the most frequently mentioned source of information about mpox by participants (63%; n=97; p<0.001). This medium was also the most preferred source of information about mpox (39%; n=60; p=0.109). The majority of participants stated that they did not know what mpox is (67.6%; n=146), and less than half knew that it is preventable (42.4%; n=89). Of those who stated that mpox is a preventable illness, less than half knew about the existence of a vaccine (44.9%; n=40; p<0.001).
CONCLUSIONS
This study provides insights into the awareness, knowledge, prevention tools and information channels of individuals who contacted the "Telefono Verde AIDS e Infezioni Sessualmente Trasmesse". Useful indications for defining future information campaigns were obtained.
PubMed: 38801199
DOI: 10.7416/ai.2024.2637 -
Patterns (New York, N.Y.) May 2024Existing antibody language models are limited by their use of unpaired antibody sequence data. A recently published dataset of ∼1.6 × 10 natively paired human...
Existing antibody language models are limited by their use of unpaired antibody sequence data. A recently published dataset of ∼1.6 × 10 natively paired human antibody sequences offers a unique opportunity to evaluate how antibody language models are improved by training with native pairs. We trained three baseline antibody language models (BALM), using natively paired (BALM-paired), randomly-paired (BALM-shuffled), or unpaired (BALM-unpaired) sequences from this dataset. To address the paucity of paired sequences, we additionally fine-tuned ESM (evolutionary scale modeling)-2 with natively paired antibody sequences (ft-ESM). We provide evidence that training with native pairs allows the model to learn immunologically relevant features that span the light and heavy chains, which cannot be simulated by training with random pairs. We additionally show that training with native pairs improves model performance on a variety of metrics, including the ability of the model to classify antibodies by pathogen specificity.
PubMed: 38800360
DOI: 10.1016/j.patter.2024.100967