Peptide-drug conjugate designated for targeted delivery to HER2-expressing cancer cells.

Targeted therapy of the highest globally incident breast cancer shall resolve the issue of off-target toxicity concurring with augmented killing of specific diseased cells. Thus, the goal of this study was to prepare a peptide-drug conjugate targeting elevated expression of HER2 receptors in breast cancer. Towards this, the rL-A9 peptide was conjugated with the chemotherapeutic drug doxorubicin (DOX) through a N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) linker. The synthesized peptide-drug conjugate, rL-A9-DOX, was characterized by mass spectrometry. Molecular docking studies, based on binding energy data, suggested a stronger interaction of rL-A9-DOX with the HER2 receptor in comparison to the unconjugated peptide, rL-A9. The cytotoxic effect of the rL-A9-DOX conjugate was observed to be higher in HER2-positive SKOV3 cells compared to HER2-negative MDA-MB-231 cells, indicating selective cell killing. Cellular internalization of the rL-A9-DOX conjugate was evident from the flow cytometry analysis, where a noticeable shift in mean fluorescent intensity (MFI) was observed for the conjugate compared to the control group. This data was further validated by confocal microscopy, where the fluorescent signal ascertained nuclear accumulation of rL-A9-DOX. The present studies highlight the promising potential of rL-A9-DOX for targeted delivery of the drug into a defined group of cancer cells.

Orally Ingested Self-Powered Stimulators for Targeted Gut-Brain Axis Electrostimulation to Treat Obesity and Metabolic Disorders.

Obesity is a significant health concern that often leads to metabolic dysfunction and chronic diseases. This study introduces a novel approach to combat obesity using orally ingested self-powered electrostimulators. These electrostimulators consist of piezoelectric BaTiO3 (BTO) particles conjugated with capsaicin (Cap) and aim to activate the vagus nerve. Upon ingestion by diet-induced obese (DIO) mice, the BTO@Cap particles specifically target and bind to Cap-sensitive sensory nerve endings in the gastric mucosa. In response to stomach peristalsis, these particles generate electrical signals. The signals travel via the gut-brain axis, ultimately influencing the hypothalamus. By enhancing satiety signals in the brain, this neuromodulatory intervention reduces food intake, promotes energy metabolism, and demonstrates minimal toxicity. Over a 3-week period of daily treatments, DIO mice treated with BTO@Cap particles show a significant reduction in body weight compared to control mice, while maintaining their general locomotor activity. Furthermore, this BTO@Cap particle-based treatment mitigates various metabolic alterations associated with obesity. Importantly, this noninvasive and easy-to-administer intervention holds potential for addressing other intracerebral neurological diseases.

Analysis of the impact of intraventricular hemorrhage on the functional outcome of ruptured anterior cerebral artery aneurysm after clipping.

Background: Various clinical symptoms and variables have been suggested as potential indicators of outcomes in patients with subarachnoid hemorrhage (SAH) resulting from ruptured intracranial aneurysms. The detailed discussion of the consequences of intraventricular hemorrhage (IVH), frequently reported in cases of anterior communicating artery (ACoA) aneurysms, is still pending. The study aimed to assess the results of aneurysm surgery performed early versus delayed in patients with SAH, specifically focusing on the occurrence of IVH. Methods: This study involved patients with ACoA aneurysms who experienced SAH and underwent microsurgical clipping of the aneurysm. A retrospective review was conducted on the patients' medical records. The modified Rankin score was compared between two groups of patients based on the presence or absence of IVH. Results: Ninety-one participants (52 males and 39 females) were included in the study. The initial computed tomography scan showed that 20 patients (with a mean age of 51 ± 13.7 years) had IVH, while 71 patients (with a mean age of 45.8 ± 11.7 years) did not have any signs of IVH. The proportion of patients with poor functional outcomes after six months was 55% in the presence of IVH, compared to 25.4% in patients without IVH, indicating a significant difference in outcome between the two groups (P < 0.016). Conclusion: Patients with SAH having aneurysms located in the ACoA associated with the intraventricular hemorrhage had a poor functional outcome.

Gelatin/Polyacrylamide-Based Antimicrobial and Self-Healing Hydrogel Film for Wound Healing Application.

In this study, a self-healing, adhesive, and superabsorbent film made of gelatin, poly(acrylamide), and boric acid (GelAA) was successfully synthesized using a free radical reaction mechanism. The optimized film showed a remarkable 2865 ± 42% water absorptivity and also exhibited excellent self-healing behavior. The GelAA films were further loaded with silver nanoclusters (AgNCs) and ursodeoxycholic acid (UDC) (loading efficiency = 10%) to develop UDC/Ag/GelAA films. The loading of AgNCs in UDC/Ag/GelAA films helped in exhibiting 99.99 ± 0.01% antibacterial activity against both Gram-positive and Gram-negative bacteria, making them very effective against bacterial infections. Additionally, UDC/Ag/GelAA films had 77.19 ± 0.52% porosity and showed 90% of UDC release in 30 h, which helps in improving the cell proliferation. Our research provides an easy but highly effective process for synthesizing a hydrogel film, which is an intriguing choice for wound healing applications without the use of antibiotics.

Harnessing HfO2 Nanoparticles for Wearable Tumor Monitoring and Sonodynamic Therapy in Advancing Cancer Care.

Addressing the critical requirement for real-time monitoring of tumor progression in cancer care, this study introduces an innovative wearable platform. This platform employs a thermoplastic polyurethane (TPU) film embedded with hafnium oxide nanoparticles (HfO2 NPs) to facilitate dynamic tracking of tumor growth and regression in real time. Significantly, the synthesized HfO2 NPs exhibit promising characteristics as effective sonosensitizers, holding the potential to efficiently eliminate cancer cells through ultrasound irradiation. The TPU-HfO2 film, acting as a dielectric elastomer (DE) strain sensor, undergoes proportional deformation in response to changes in the tumor volume, thereby influencing its electrical impedance. This distinctive behavior empowers the DE strain sensor to continuously and accurately monitor alterations in tumor volume, determining the optimal timing for initiating HfO2 NP treatment, optimizing dosages, and assessing treatment effectiveness. Seamless integration with a wireless system allows instant transmission of detected electrical impedances to a smartphone for real-time data processing and visualization, enabling immediate patient monitoring and timely intervention by remote medical staff. By combining the dynamic tumor monitoring capabilities of the TPU-HfO2 film with the sonosensitizer potential of HfO2 NPs, this approach propels cancer care into the realm of telemedicine, representing a significant advancement in patient treatment.

Poison in the water: Arsenic's silent assault on fish health.

Arsenic occurs across the world in freshwater and marine environments, menacing the survival of aquatic organisms. Organic and inorganic forms of this substance can be found, in which the inorganic form is more hazardous than the organic form. Most aquatic bodies contain inorganic arsenic species, but organic species are believed to be the dominant form of arsenic in the majority of fish. Natural and anthropogenic both are the sources of water contamination with arsenic. Its bioaccumulation and transfer from one trophic level to another in the aquatic food chain make arsenic a vital environmental issue. Continuous exposure to low concentrations of arsenic in aquatic organisms including fish leads to its bioaccumulation, which may affect organisms of higher trophic levels including large fishes or humans. Humans can be exposed to arsenic through the consumption of fish contaminated with arsenic. Hence, the present review facilitates our understanding about sources of arsenic, its bioaccumulation, food chain transfer, and its effect on the fish health. Also, "Poison in the Water: Arsenic's Silent Assault on Fish Health" serves as a wake-up call to recognize the pressing need to address arsenic contamination in water bodies. By understanding its devastating impact on fish health, we can strive to implement sustainable practices and policies that safeguard our precious aquatic environments and ensure the well-being of both wildlife and human communities that depend on them.

Natural flavonoid pectolinarin computationally targeted as a promising drug candidate against SARS-CoV-2.

Coronavirus disease-2019 (COVID-19) has become a global pandemic, necessitating the development of new medicines. In this investigation, we identified potential natural flavonoids and compared their inhibitory activity against spike glycoprotein, which is a target of SARS-CoV-2 and SARS-CoV. The target site for the interaction of new inhibitors for the treatment of SARS-CoV-2 has 82% sequence identity and the remaining 18% dissimilarities in RBD S1-subunit, S2-subunit, and 2.5% others. Molecular docking was employed to analyse the various binding processes used by each ligand in a library of 85 natural flavonoids that act as anti-viral medications and FDA authorised treatments for COVID-19. In the binding pocket of the target active site, remdesivir has less binding interaction than pectolinarin, according to the docking analysis. Pectolinarin is a natural flavonoid isolated from Cirsiumsetidensas that has anti-cancer, vasorelaxant, anti-inflammatory, hepatoprotective, anti-diabetic, anti-microbial, and anti-oxidant properties. The S-glycoprotein RBD region (330-583) is inhibited by kaempferol, rhoifolin, and herbacetin, but the S2 subunit (686-1270) is inhibited by pectolinarin, morin, and remdesivir. MD simulation analysis of S-glycoprotein of SARS-CoV-2 with pectolinarin complex at 100ns based on high dock-score. Finally, ADMET analysis was used to validate the proposed compounds with the highest binding energy.

Corrigendum: Fabrication and evaluation of herbal beads to slow cell ageing.

[This corrects the article DOI: 10.3389/fbioe.2022.1025405.].

Metagenomic analysis reveals diverse microbial community and potential functional roles in Baner rivulet, India.

BACKGROUND: The health index of any population is directly correlated with the water quality, which in turn depends upon physicochemical characteristics and the microbiome of that aquatic source. For maintaining the water quality, knowledge of microbial diversity is a must. The present investigation attempts to evaluate the microflora of Baner. Metagenomics has been proven to be the technique for examining the genetic diversity of unculturable microbiota without using traditional culturing techniques. The microbial profile of Baner is analyzed using metagenomics for the first time to the best of our knowledge. RESULTS: To explore the microbial diversity of Baner, metagenomics analysis from 3 different sites was done. Data analysis identified 29 phyla, 62 classes, 131 orders, 268 families, and 741 genera. Proteobacteria was found to be the most abundant phylum in all the sampling sites, with the highest abundance at S3 sampling site (94%). Bacteroidetes phylum was found to be second abundant in S1 and S2 site, whereas Actinobacteria was second dominant in sampling site S3. Enterobacteriaceae family was dominant in site S1, whereas Comamonadaceae and Pseudomonadaceae was abundant in sites S2 and S3 respectively. The Baner possesses an abundant bacterial profile that holds great promise for developing bioremediation tactics against a variety of harmful substances. CONCLUSION: Baner river's metagenomic analysis offers the first insight into the microbial profile of this hilly stream. Proteobacteria was found to be the most abundant phylum in all the sampling sites indicating anthropogenic interference and sewage contamination. The highest abundance of proteobacteria at S3 reveals it to be the most polluted site, as it is the last sampling site downstream of the area under investigation, and falls after crossing the main city, so more human intervention and pollution were observed. Despite some pathogens, a rich profile of bacteria involved in bioremediation, xenobiotic degradation, and beneficial fish probiotics was observed, reflecting their potential applications for improving water quality and establishing a healthy aquaculture and fishery section.

Adsorptive removal of oxytetracycline using MnO2-engineered pine-cone biochar: thermodynamic and kinetic investigation and process optimization.

Indiscriminate use of oxytetracycline is linked to the development of antibiotic-resistant genes, posing a serious threat to human health and ecosystem balance. This article reports the adsorptive elimination of oxytetracycline (OTC) from aqueous solution using a newly developed MnO2-modified pine-cone biochar (MnO2/PCBC). The MnO2/PCBC was characterized using X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, CHNS analyzer, inductively coupled plasma-optical emission spectroscopy, and Brunauer-Emmett-Teller N2 adsorption analyzer. Batch adsorption experiments, designed using the central composite design framework of response surface methodology, were conducted to investigate the influence of process variables on the adsorption of OTC onto MnO2/PCBC. The optimized conditions for achieving maximum removal (88.1%) were found to be at pH 8, MnO2/PCBC dose 0.44 g/L, initial OTC concentration 200 mg/L, and temperature 303 K. The adsorption process follows Langmuir (R2=0.95) and Freundlich (R2=0.95) isotherms and pseudo-second-order (R2=0.99) adsorption kinetics. The adsorption process was found to be endothermic (ΔH0 = 33.04 kJ/mol) and spontaneous in nature (ΔG0 from -1.33 kJ/mol at 283 K to -5.65 kJ/mol at 313 K). The synthesized MnO2/PCBC could be recycled and reused for OTC removal with a percentage removal of around 80% after fifth cycle. The results indicate an effective removal of oxytetracycline with only 0.44 g/L MnO2/PCBC with maximum adsorption capacity of 357.14 mg/g which demonstrates improved performance in comparison to many adsorbents reported in literature. This implies that MnO2/PCBC offers potential to be developed into a cost-effective technique for antibiotic removal from water.

Regulation of omega-3 fatty acids production by different genes in freshwater fish species: a review.

The present study aims to compare the gene expression of three different fish species (common carp, tilapia, and trout) with varying levels of fatty acids (FA). Based on transcriptome analysis and RNA sequencing, various genes and their associated metabolic pathways are identified. Pathways are categorized based on the genes they encode. Genes that were differentially expressed and their promoter's methylation patterns were revealed by RNA-seq analysis in common carp. Furthermore, fatty acid-enriched pathways, such as ARA4 and adipocytokine signaling, were also identified. Many genes and pathways may influence tilapia's growth and omega-3 content. Using the mTOR pathway, trout with differential expression were discovered to be involved in producing omega-3 fatty acids. This study revealed major pathways in fish species to produce omega-3 fatty acids.

Comparative and clinical evaluation between piezoelectric and conventional rotary techniques for mandibular impacted third molar extraction.

Purpose: The aim of this study was to evaluate and compare the operative and postoperative outcomes of the mandibular impacted third molar removal using piezoelectric technique and conventional rotary bur technique. Settings: The study was conducted in the department of oral and maxillofacial surgery between January 1, 2019, and January 1, 2020. Materials and Methods: Thirty patients, with an age of 18-40 years, with asymptomatic bilateral impacted mandibular third molars, were selected for the study and randomly surgical extraction was done either using piezoelectric or the conventional rotary bur technique on each site. The intraoperative time taken, postoperative pain, swelling, and trismus were assessed over a follow-up period of 7 days postoperatively. Results: Study and control groups were compared using paired t-test. There was statistical significance in reduction of pain and swelling in the study group where the duration of surgery was increased in the study group. Conclusion: Even if piezoelectric technique takes more time but can be used safely as another technique to conventional surgical method with surgical bur and handpiece for removal of impacted mandibular third molars.

A critical review on biochar production from pine wastes, upgradation techniques, environmental sustainability, and challenges.

Pine wastes, including pine needles, cones, and wood, are abundantly produced as an agroforestry by-product globally and have shown tremendous potential for biochar production. Various thermochemical conversion technologies have exhibited promising results in converting pine wastes to biochar, displaying impressive performance. Hence, this review paper aims to investigate the possibilities and recent technological advancements for synthesizing biochar from pine waste. Furthermore, it explores techniques for enhancing the properties of biochar and its integrated applications in various fields, such as soil and water remediation, carbon sequestration, battery capacitor synthesis, and bio-coal production. Finally, the paper sheds light on the limitations of current strategies, emphasizing the need for further research and study to address the challenges in pine waste-based biochar synthesis. By promoting sustainable and effective utilization of pine wastes, this review contributes to environmental conservation and resource management.

Repurposing the single-used-plastic for development of hydrophobic aerogels for remediation of oil spill and organic solvents.

Currently, around 400 million tonnes of synthetic polymers are being dumped as waste annually and by this rate by 2050 the ocean would contain more such waste compared to the total weight of fish. As recycling could solve part of this problem, recently such waste is being reused for various purposes like composite preparation, oil production and various other use such as production of foams, sponges, and aerogels. However, there is a relatively limited literature available on the utilization of polyethylene polymer (like LDPE). The study presented in this article indicated that LDPE-based polymers could be reused (after modification) for preparation of hydrophobic, lightweight, and porous aerogels that have oil-spills and organic solvent adsorption capacity. The aerogels showed contact angle of 121.9o, bulk density below 0.25 g/cm3, and were found to be semi-crystalline. The aerogels showed oil and solvent adsorption more than that for their untreated counterparts. Also, the aerogels were found to be recycled for more than five cycles with very minimum loss of efficacy. This area of producing oil sorbents from single used plastic wastes is still very open for further research and seems to be a promising route for both waste reduction, and the synthesis of value-added products. This could be one of the most sustainable approaches for efficient single-used plastic wase management and environment clean-up.

Synthesis and 177Lu Labeling of the First Retro Analog of the HER2-Targeting A9 Peptide: A Superior Variant.

The retro analog of the HER2-targeting A9 peptide was synthesized by coupling amino acids in a reverse fashion and switching the N-terminal in the original sequence of the L-A9 peptide (QDVNTAVAW) to the C-terminal in rL-A9 (WAVATNVDQ). Modification in the backbone resulted in higher conformational stability of the retro peptide as evident from CD spectra. Molecular docking analysis revealed a higher HER2 binding affinity of [177Lu]Lu-DOTA-rL-A9 than the original radiopeptide [177Lu]Lu-DOTA-L-A9. Enormously enhanced metabolic stability of the retro analog led to significant elevation in tumor uptake and retention. SPECT imaging studies corroborated biodistribution results demonstrating a remarkably higher tumor signal for [177Lu]Lu-DOTA-rL-A9. The presently studied retro probe has promising efficiency for clinical screening.

Current Trends in Nanotheranostics: A Concise Review on Bioimaging and Smart Wearable Technology.

The area of interventional nanotheranostics combines the use of interventional procedures with nanotechnology for the detection and treatment of physiological disorders. Using catheters or endoscopes, for example, interventional techniques make use of minimally invasive approaches to diagnose and treat medical disorders. It is feasible to increase the precision of these approaches and potency by integrating nanotechnology. To visualize and target various parts of the body, such as tumors or obstructed blood veins, one can utilize nanoscale probes or therapeutic delivery systems. Interventional nanotheranostics offers targeted, minimally invasive therapies that can reduce side effects and enhance patient outcomes, and it has the potential to alter the way that many medical illnesses are handled. Clinical enrollment and implementation of such laboratory scale theranostics approach in medical practice is promising for the patients where the user can benefit by tracking its physiological state. This review aims to introduce the most recent advancements in the field of clinical imaging and diagnostic techniques as well as newly developed on-body wearable devices to deliver therapeutics and monitor its due alleviation in the biological milieu.

Key oncologic pathways inhibited by Erinacine A: A perspective for its development as an anticancer molecule.

In the modern era, cancer can be controlled by chemotherapy treatment, and in many situations a stable disease is obtained. The significant clinical success and subsequent commercialization of naturally derived molecules have further encouraged their exploration as adjunctive therapies in cancer management. The purpose of this comprehensive review is to update the anticancer mechanisms triggered by Erinacine A and regulation of signaling pathways potentially involved in its anticancer activity.The results of preclinical research showed that Erinacin A, a therapeutically important biological metabolite isolated from the basidiomycete fungus Hericium erinaceus offers a multitude of possible chemotherapeutic applications by regulating complex signaling pathways as validated by various pharmacological in vitro and in vivo studies. As a result of Erinacin A's action on oncological signaling pathways, it resulted in induction of apoptosis, reduction of proliferation, invasiveness, generation of oxidative stress and cell cycle arrest in cancer cells.

Loss of CpFTSY Reduces Photosynthetic Performance and Affects Insertion of PsaC of PSI in Diatoms.

The chloroplast signal recognition particle (CpSRP) receptor (CpFTSY) is a component of the CpSRP pathway that post-translationally targets light-harvesting complex proteins (LHCPs) to the thylakoid membranes in plants and green algae containing chloroplasts derived from primary endosymbiosis. In plants, CpFTSY also plays a major role in the co-translational incorporation of chloroplast-encoded subunits of photosynthetic complexes into the thylakoids. This role has not been demonstrated in green algae. So far, its function in organisms with chloroplasts derived from secondary endosymbiotic events has not been elucidated. Here, we report the generation and characterization of mutants lacking CpFTSY in the diatom Phaeodactylum tricornutum. We found that this protein is not involved in inserting LHCPs into thylakoid membranes, indicating that the post-translational part of the CpSRP pathway is not active in this group of microalgae. The lack of CpFTSY caused an increased level of photoprotection, low electron transport rates, inefficient repair of photosystem II (PSII), reduced growth, a strong decline in the PSI subunit PsaC and upregulation of proteins that might compensate for a non-functional co-translational CpSRP pathway during light stress conditions. The phenotype was highly similar to the one described for diatoms lacking another component of the co-translational CpSRP pathway, the CpSRP54 protein. However, in contrast to cpsrp54 mutants, only one thylakoid membrane protein, PetD of the Cytb6f complex, was downregulated in cpftsy. Our results point to a minor role for CpFTSY in the co-translational CpSRP pathway, suggesting that other mechanisms may partially compensate for the effect of a disrupted CpSRP pathway.