Eukaryotic translation elongation factors 1 alpha, eEF1A1 and eEF1A2, are not only translation factors but also pleiotropic proteins that are highly expressed in human tumors, including breast ...cancer, ovarian cancer, and lung cancer. eEF1A1 modulates cytoskeleton, exhibits chaperone-like activity and also controls cell proliferation and cell death. In contrast, eEF1A2 protein favors oncogenesis as shown by the fact that overexpression of eEF1A2 leads to cellular transformation and gives rise to tumors in nude mice. The eEF1A2 protein stimulates the phospholipid signaling and activates the Akt-dependent cell migration and actin remodeling that ultimately favors tumorigenesis. In contrast, inactivation of eEF1A proteins leads to immunodeficiency, neural and muscular defects, and favors apoptosis. Finally, eEF1A proteins interact with several viral proteins resulting in enhanced viral replication, decreased apoptosis, and increased cellular transformation. This review summarizes the recent findings on eEF1A proteins indicating that eEF1A proteins play a critical role in numerous human diseases through enhancement of oncogenesis, blockade of apoptosis, and increased viral pathogenesis.
HIV-1 latency in monocytes/macrophages Kumar, Amit; Abbas, Wasim; Herbein, Georges
Viruses,
04/2014, Letnik:
6, Številka:
4
Journal Article, Book Review
Recenzirano
Odprti dostop
Human immunodeficiency virus type 1 (HIV-1) targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence ...of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART) has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host.
Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and a significant global health burden, with increasing incidence rates and limited treatment options. Immunotherapy has become a ...promising approach due to its ability to affect the immune microenvironment and promote antitumor responses. The immune microenvironment performs an essential role in both the progression and the development of HCC, with different characteristics based on specific immune cells and etiological factors. Immune checkpoint inhibitors, including programmed death-1/programmed death-ligand 1 inhibitors (pembrolizumab, nivolumab, and durvalumab) and cytotoxic T lymphocyte antigen-4 inhibitors (tremelimumab and ipilimumab), have the potential to treat advanced HCC and overcome adverse effects, such as liver failure and chemoresistance. Phase II and phase III clinical trials highlight the efficacy of pembrolizumab and nivolumab, respectively, in advanced HCC patients, as demonstrated by their positive effects on overall survival and progression-free survival. Tremelimumab has exhibited modest response rates, though it does possess antiviral activity. Thus, it is still being investigated in ongoing clinical trials. Combination therapies with multiple drugs have demonstrated potential benefits in terms of survival and tumor response rates, improving patient outcomes compared to monotherapy, especially for advanced-stage HCC. This review addresses the clinical trials of immunotherapies for early-, intermediate-, and advanced-stage HCC. Additionally, it highlights how combination therapy can significantly enhance overall survival, progression-free survival, and objective response rate in advanced-stage HCC, where treatment options are limited.
Studying how traditional knowledge regarding wild food plants and particularly wild vegetables changes over time and space is crucial for understanding which socio-ecological variables may have an ...influence on traditional foraging behaviors. Recent work has found that religious affiliation may play a central role since, in specific cultural contexts, religion shapes kinship relations and consequently the vertical transmission of traditional knowledge and practices. In order to further test this hypothesis, a field ethnobotanical study specifically focusing on wild vegetables was conducted among four religious communities (Shias, Sunnis, Christians, and Sikhs) in Kurram District, North-West Pakistan. Results show that a remarkable bio-cultural heritage comprising fifty-five folk wild food taxa survives today; most of the wild plants were however quoted by few informants, suggesting that this traditional knowledge system is possibly under threat. More than the half of the quoted wild vegetables were not yet reported so far in the Pakistan wild food ethnobotanical literature. The most commonly gathered wild vegetables were
Amaranthus viridis
L.
, Margarospermum officinale
L.
, Malva neglecta
Wallr.,
Portulaca oleracea
L., and
Rumex dentatus
L. Most of the recorded wild vegetables were quoted by Shia and, to less extent, by Sunni community members, while Christians and Sikhs showed an extremely restricted wild plant food repertoire. These differences may be related to the different history and socio-economic conditions of the considered religious groups, to geographical/ecological factors and probably to the very specific origin of the Shia groups (Turi tribe) of the region, which moved from Western Asia a few centuries ago. Moreover, a remarkable portion of the quoted wild vegetables are perceived to have specific medicinal properties. A serious reconsideration of the recorded wild food plant resources, especially also within educational platforms, could be crucial for fostering culturally-appropriate food security strategies in marginal areas of Pakistan.
On May 4, 2023, four schoolteachers and four drivers, including the young ethnobotanist Sayed Hussain, lost their lives at their school, massacred by religious extremists in the village of Teri ...Mangal, Kurram District, NW Pakistan, near the Pakistani-Afghan border. Ethnobiologists working in this area believe in the power of education and community-centered rural development as prominent tools for bringing about decent sustainable livelihoods in the near future and ultimately fostering social cohesion, tolerance, and peace. Ethnobiology was expressly conceived and designed to play a pivotal role in celebrating the richness of diversity of both indigenous and minority groups and especially to stop their oppression and discrimination, building the conditions for providing them true agency in their inalienable right to shape a decent future for their children. Field ethnobiologists in Kurram feel the palpable social tension, the fears local people confront daily and even sometimes the reluctance of a few community members to discuss and share their folk knowledge, while at other times, the burden of accessing militarily controlled areas and territories affected by landmines made their field research unfeasible. Nevertheless, ethnobiologists conducting field studies and navigating through these major difficulties exercise their daily resilience daily and believe in the power of the continuous dialogue between local knowledge holders and scholars.
Human immunodeficiency virus type 1 (HIV-1) establishes latency in resting memory CD4+ T cells and cells of myeloid lineage. In contrast to the T cells, cells of myeloid lineage are resistant to the ...HIV-1 induced cytopathic effect. Cells of myeloid lineage including macrophages are present in anatomical sanctuaries making them a difficult drug target. In addition, the long life span of macrophages as compared to the CD4+ T cells make them important viral reservoirs in infected individuals especially in the late stage of viral infection where CD4+ T cells are largely depleted. In the past decade, HIV-1 persistence in resting CD4+ T cells has gained considerable attention. It is currently believed that rebound viremia following cessation of combination anti-retroviral therapy (cART) originates from this source. However, the clinical relevance of this reservoir has been questioned. It is suggested that the resting CD4+ T cells are only one source of residual viremia and other viral reservoirs such as tissue macrophages should be seriously considered. In the present review we will discuss how macrophages contribute to the development of long-lived latent reservoirs and how macrophages can be used as a therapeutic target in eradicating latent reservoir.
In a long-lasting major disease outbreak such as that of COVID-19, the challenge for public health authorities is to keep people motivated and keen on following safety guidelines. In this study, a ...compartmental model with a heterogeneous transmission rate (based on awareness) is utilized to hypothesize about the public adoption of preventive guidelines. Three subsequent outbreaks in South Korea, Pakistan, and Japan were analyzed as case studies. The transmission, behavior change, and behavioral change ease rates of the disease were measured in these countries. The parameters were estimated using the maximum likelihood method with an additional identifiability analysis performed to determine the uniqueness of the estimated parameters for quantitatively comparing them during the first three waves of COVID-19. The mathematical analysis and simulation results show that individual responses had a significant effect on the outbreak. Individuals declining to follow the public health guidelines in Korea and Japan between the second and third waves contributed to making the third peak the highest of the three peaks. In Pakistan, however, individual responses to following public health guidelines were maintained between the second and third waves, resulting in the third peak being lower than the first, rather than being associated with the highest transmission rate. Thus, maintaining a high level of awareness is critical for containing the spread. Improvised public health campaigns are recommended to sustain individual attention and maintain a high level of awareness.
The foot-and-mouth disease virus is a highly contagious and economically devastating virus of cloven-hooved animals, including cattle, buffalo, sheep, and goats, causing reduced animal productivity ...and posing international trade restrictions. For decades, chemically inactivated vaccines have been serving as the most effective strategy for the management of foot-and-mouth disease. Inactivated vaccines are commercially produced in cell culture systems, which require successful propagation and adaptation of field isolates, demanding a high cost and laborious time. Cell culture adaptation is chiefly indebted to amino acid substitutions in surface-exposed capsid proteins, altering the necessity of RGD-dependent receptors to heparan sulfate macromolecules for virus binding. Several amino acid substations in VP1, VP2, and VP3 capsid proteins of FMDV, both at structural and functional levels, have been characterized previously. This literature review combines frequently reported amino acid substitutions in virus capsid proteins, their critical roles in virus adaptation, and functional characterization of the substitutions. Furthermore, this data can facilitate molecular virologists to develop new vaccine strains against the foot-and-mouth disease virus, revolutionizing vaccinology via reverse genetic engineering and synthetic biology.
Tumor necrosis factor (TNF) and TNF receptors (TNFR) superfamily members are engaged in diverse cellular phenomena such as cellular proliferation, morphogenesis, apoptosis, inflammation, and immune ...regulation. Their role in regulating viral infections has been well documented. Viruses have evolved with numerous strategies to interfere with TNF-mediated signaling indicating the importance of TNF and TNFR superfamily in viral pathogenesis. Recent research reports suggest that TNF and TNFRs play an important role in the pathogenesis of HIV. TNFR signaling modulates HIV replication and HIV proteins interfere with TNF/TNFR pathways. Since immune activation and inflammation are the hallmark of HIV infection, the use of TNF inhibitors can have significant impact on HIV disease progression. In this review, we will describe how HIV infection is modulated by signaling mediated through members of TNF and TNFR superfamily and in turn how these latter could be targeted by HIV proteins. Finally, we will discuss the emerging therapeutics options based on modulation of TNF activity that could ultimately lead to the cure of HIV-infected patients.
Two eggplant cultivars, Dilnasheen and Bemisal, were selected to assess whether pure GB and sugarbeet extract could effectively ameliorate the harmful effects of salt stress on eggplant (
Solanum ...melongena L.), under saline conditions. Salt stress markedly suppressed the growth, yield, photosynthetic capacity, internal CO
2 level, transpiration, and stomatal conductance in both cultivars. Potassium (K
+) and Ca
2+ contents and K
+/Na
+ ratios of both root and leaf were also reduced, while GB and proline in leaves, and Na
+ and Cl
− contents in roots and leaves were significantly enhanced. Exogenously applied glycinebetaine and sugarbeet extracts significantly counteracted the salt-induced adverse effects on growth, yield, various gas exchange characteristics, GB and leaf K
+, Ca
+, Cl
− and Na
+. However, GB and sugarbeet extract showed differential effects on photosynthetic rate, stomatal conductance and transpiration, internal CO
2 level,
C
i
/C
a
ratio, leaf K
+, Ca
2+, and Cl
− contents, and K
+/Na
+ ratio. Sugarbeet extract proved better than the GB in improving growth, photosynthetic rate, transpiration, stomatal conductance, yield and GB accumulation. Since, sugarbeet extract contains a substantial amount of GB along with a variety of other important nutrients so it was found as effective as pure GB in improving growth and some key physiological processes in eggplant under salt stress. Thus, it can be used as an alternative cheaper source of GB for its use as an ameliorative agent for protecting plants against the hazardous effects of salt stress.
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