Aptamer as a targeted approach towards treatment of breast cancer.

Aptamers, a novel type of targeted ligand used in drug delivery, have quickly gained popularity due to their high target specificity and affinity. Different aptamer-mediated drug delivery systems, such as aptamer-drug conjugate (ApDC), aptamer-siRNA, and aptamer-functionalised nanoparticle systems, are currently being developed for the successful treatment of cancer based on the excellent properties of aptamers. These systems can decrease potential toxicity and enhance therapeutic efficacy by targeting the drug moiety. In this review, we provide an overview of recent developments in aptamer-mediated delivery systems for cancer therapy, specifically for breast cancer, and talk about the potential applications and current issues of novel aptamer-based techniques. This study in aptamer technology for breast cancer therapy highlights key aptamers targeting well-established biomarkers such as HER2, oestrogen receptor, and progesterone receptor. Additionally, we explore the potential of aptamers in overcoming various challenges such as drug resistance and improving the delivery of therapeutic agents. This review aims to provide a deeper understanding of the present aptamer-based targeted delivery applications through in-depth analysis to increase efficacy and create new therapeutic approaches that may ultimately lead to better treatment outcomes for cancer patients.

Nosocomial infections by diverse carbapenemase-producing Aeromonas hydrophila associated with combination of plumbing issues and heat waves.

BACKGROUND: Aquatic opportunistic pathogen Aeromonas hydrophila, known to persist in low-nutrient chlorinated waters, can cause life-threatening infections. Two intensive care units experienced a cluster of Aeromonas infections following outdoor temperature spikes coinciding with recurrent plumbing issues, with fatalities due to severe underlying comorbidities co-occurring with extensively-drug resistant (XDR) Aeromonas. METHODS: We investigated this cluster using whole genome sequencing to assess genetic relatedness of isolates and identify antimicrobial resistance determinants. Three A. hydrophila were isolated from patients staying in or adjacent to rooms with plumbing issues during or immediately after periods of elevated outdoor temperatures. Sinks and faucets were swabbed for culture. RESULTS: All A. hydrophila clinical isolates exhibited carbapenem resistance but were not genetically related. Diverse resistance determinants corresponding to extensively-drug resistant were found, including co-occurring KPC-3 and VIM-2, OXA-232, and chromosomal CphA-like carbapenemase genes, contributing to major treatment challenges. All 3 patients were treated with multiple antibiotic regimens to overcome various carbapenemase classes and expired due to underlying comorbidities. Environmental culture yielded no Aeromonas. CONCLUSIONS: While the investigation revealed no singular source of contamination, it supports a possible link between plumbing issues, elevated outdoor temperatures and incidence of nosocomial Aeromonas infections. The diversity of carbapenemase genes detected in these wastewater-derived Aeromonas warrants heightened infection prevention precautions during periods of plumbing problems especially with heat waves.

The impact of COVID-19 and masking practices on pertussis cases at a large academic medical center (2019-2021).

We reviewed cases of Bordatella pertussis (B. pertussis) cases in ambulatory clinics at a large academic health care institution in Los Angeles from 2019-2021. Public health prevention measures during the Coronavirus disease 19 (COVID-19) pandemic impacted the number of pertussis cases identified.

Vaccine-Associated Measles in a Hematopoietic Cell Transplant Recipient: Case Report and Comprehensive Review of the Literature.

Measles is a worldwide viral disease that can cause fatal complications in immunocompromised hosts such as hematopoietic cell transplant (HCT) recipients. The live attenuated measles, mumps, and rubella (MMR) vaccine is generally contraindicated post-HCT due to the risk for vaccine-associated measles. This, combined with decreasing vaccination rates due to vaccine hesitancy and the coronavirus disease 2019 pandemic, raises significant concerns for a measles resurgence that could portend devastating consequences for immunocompromised hosts. Multiple guidelines have included criteria to determine which HCT recipients can safely receive the MMR vaccine. Here, we report a case of vaccine-associated measles in a HCT recipient who met guideline-recommended criteria for MMR vaccination. The objective of this article is to query these criteria, highlight the importance of MMR vaccination, and comprehensively review the literature.

l-3,4-Dihydroxyphenylalanine templated anisotropic gold nano/micro-roses as potential disrupters/inhibitors of α-crystallin protein and its gleaned model peptide aggregates.

Cataract, the major cause of blindness worldwide occurs due to the misfolding and aggregation of the protein crystallin, which constitute a major portion of the lens protein. Other than the whole protein crystallin, the peptide sequences generated from crystallin as a result of covalent protein damage have also been shown to possess and foster protein aggregation, which can be established as crystallin aggregation models. Thus, the disaggregation or inhibition of these protein aggregates could be a viable approach to combat cataract and preserve lens proteostasis. Herein, we tried to explore the disruption as well as inhibition of the intact α-crystallin protein and α-crystallin derived model peptide aggregates by l-3,4-dihydroxyphenylalanine (levodopa) coated gold (Au) nano/micro-roses as modulators. Thioflavin T fluorescence enhancement assay, and electron microscopic analysis were being employed to probe the anti-aggregation behavior of the Au nano/micro-roses towards the aggregating α-crystallin peptides/protein. Further, computational studies were performed to reveal the nature of molecular interactions between the levodopa molecule and the α-crystallin derived model peptides. Interestingly, both levodopa coated Au nano/micro-roses were found to be capable of inhibiting as well as preventing the aggregation of the intact α-crystallin protein and other model peptides derived from it.

Carrier-free self-built aspirin nanorods as anti-aggregation agents towards alpha-crystallin-derived peptide aggregates: potential implications in non-invasive cataract therapy.

The aggregation of the α-crystallin protein is the pathological hallmark of cataract. In the current work, peptide fragments derived from native α-crystallin were synthesized and explored as a peptide-based crystallin aggregation model towards cataract. The anti-aggregation potential of aspirin was evaluated towards these peptide-generated aggregates as well as towards the α-crystallin aggregate. The results demonstrated that aspirin had the capacity to inhibit crystallin and crystallin-derived peptide aggregation and could act as a potential therapeutic agent in mitigating cataract. Computational studies were also carried out to study the interaction between the model peptides and aspirin. The results revealed the existence of molecular interactions between the peptides and aspirin, which had a significant impact on the secondary structure of the peptides and potentially modulated their assembly and aggregation behavior. The formation of self-built aspirin nanorods was also explored and their ability to inhibit the aggregation of model cataract peptides and α-crystallin aggregation was validated. These findings open up the possibility of using small molecule-based nanotherapeutics for cataract merely through topical applications, which can be beneficial to cataract patients.

Cholesterol bound Plasmodium falciparum co-chaperone 'PFA0660w' complexes with major virulence factor 'PfEMP1' via chaperone 'PfHsp70-x'.

Lethality of Plasmodium falciparum caused malaria results from 'cytoadherence', which is mainly effected by exported Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. Several exported P. falciparum proteins (exportome) including chaperones alongside cholesterol rich microdomains are crucial for PfEMP1 translocation to infected erythrocyte surface. An exported Hsp40 (heat shock protein 40) 'PFA0660w' functions as a co-chaperone of 'PfHsp70-x', and these co-localize to specialized intracellular mobile structures termed J-dots. Our studies attempt to understand the function of PFA0660w-PfHsp70-x chaperone pair using recombinant proteins. Biochemical assays reveal that N and C-terminal domains of PFA0660w and PfHsp70-x respectively are critical for their activity. We show the novel direct interaction of PfHsp70-x with the cytoplasmic tail of PfEMP1, and binding of PFA0660w with cholesterol. PFA0660w operates both as a chaperone and lipid binding molecule via its separate substrate and cholesterol binding sites. PfHsp70-x interacts with cholesterol bound PFA0660w and PfEMP1 simultaneously in vitro to form a complex. Collectively, our results and the past literature support the hypothesis that PFA0660w-PfHsp70-x chaperone pair assists PfEMP1 transport across the host erythrocyte through cholesterol containing 'J-dots'. These findings further the understanding of PfEMP1 export in malaria parasites, though their in vivo validation remains to be performed.

Plasmodium falciparum protein 'PfJ23' hosts distinct binding sites for major virulence factor 'PfEMP1' and Maurer's cleft marker 'PfSBP1'.

Plasmodium falciparum (Pf) proteins exported to infected erythrocytes are key effectors of malaria pathogenesis. These include the PfEMP1 (Pf erythrocyte membrane protein 1) protein family that affects malaria-related mortality through cytoadhesion and parasite immune evasion. Parasites also induce membranous structures called Maurer's clefts (MC) in infected erythrocytes to compensate the lack of host protein synthetic and export machinery. PfEMP1 export is mediated by a myriad of proteins including Pf skeleton binding protein 1 (PfSBP1) and PF70, a hypothetical 16 family member. Here, we aim to understand the function of the only other exported PEXEL-positive hyp16 member 'PfJ23'. Our in vitro and in silico data suggest this protein to be mostly α-helical while displaying different oligomeric forms under reducing and non-reducing conditions. We show coherent expression, partial co-localization and direct interaction of purified PfSBP1 with recombinant and native PfJ23. Recombinant and parasite-expressed PfJ23 also bind to the cytoplasmic tail of PfEMP1, and they seem to partly co-localize during parasite development. Both novel binding partners interact simultaneously with PfJ23 in vitro to form a complex. Our results suggest a probable role for PfJ23 in export of PEXEL-negative proteins like PfSBP1 and PfEMP1, furthering our understanding of malaria biology.

PHISTc protein family members localize to different subcellular organelles and bind Plasmodium falciparum major virulence factor PfEMP-1.

Plasmodium falciparum encodes a novel repertoire of the Plasmodium helical interspersed subtelomeric (PHIST) family of exported proteins, which play diverse roles in infected red blood cells, contributing to malaria pathogenesis. PHIST proteins are central to parasite biology and modify human erythrocytes by interacting with parasite and host proteins. Here, we have attempted to understand the localization and function of two unexplored proteins of the PHISTc subfamily, PFD1140w and PF11_0503, and compared these with a well-characterized member, PFI1780w. We demonstrate that Phist domains assume different oligomeric states owing to a distinct array of subunit interface residues. Colocalization of a Maurer's cleft signature protein, P. falciparum skeleton-binding protein-1 (PfSBP-1), and P. falciparum erythrocyte membrane protein-1 (PfEMP-1) revealed different subcellular destinations for these PHIST members. We further show the binding of recombinant PHIST proteins to the cytoplasmic tail of PfEMP-1 and a novel interaction with PfSBP-1. Interestingly, PFD1140w interacts with PfEMP-1 and PfSBP-1 simultaneously in vitro leading to formation of a complex. These two distant PHISTc members also bind PfEMP-1 on distinct sites, despite sharing the Phist domain. Our data re-emphasize a supportive role for PHIST proteins in cytoadhesion, and identify a new binding partner, PfSBP-1, for members of this family. This information therefore adds another chapter to the understanding of P. falciparum biology and highlights the significance of the unexplored PHIST family.