Isolation and Characterization of Neutralizing Monoclonal Antibodies from a Large Panel of Murine Antibodies against RBD of the SARS-CoV-2 Spike Protein.

The COVID-19 pandemic, once a global crisis, is now largely under control, a testament to the extraordinary global efforts involving vaccination and public health measures. However, the relentless evolution of SARS-CoV-2, leading to the emergence of new variants, continues to underscore the importance of remaining vigilant and adaptable. Monoclonal antibodies (mAbs) have stood out as a powerful and immediate therapeutic response to COVID-19.

A linear DNA encoding the SARS-CoV-2 receptor binding domain elicits potent immune response and neutralizing antibodies in domestic cats.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of the COVID-19 pandemic, has been shown to infect a wide range of animal species, especially mammals, and besides human-to-human transmission, human-to-animal transmission has also been observed in some wild animals and pets, especially in cats. It has been demonstrated that cats are permissive to COVID-19 and are susceptible to airborne infections. Given the high transmissibility potential of SARS-CoV-2 to different host species and the close contact between humans and animals, it is crucial to find mechanisms to prevent the transmission chain and reduce the risk of spillover to susceptible species.

A first-in-human trial on the safety and immunogenicity of COVID-eVax, a cellular response-skewed DNA vaccine against COVID-19.

The COVID-19 pandemic and the need for additional safe, effective, and affordable vaccines gave new impetus into development of vaccine genetic platforms. Here we report the findings from the phase 1, first-in-human, dose-escalation study of COVID-eVax, a DNA vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Sixty-eight healthy adults received two doses of 0.

Persistent B cell memory after SARS-CoV-2 vaccination is functional during breakthrough infections.

Breakthrough SARS-CoV-2 infections in fully vaccinated individuals are considered a consequence of waning immunity. Serum antibodies represent the most measurable outcome of vaccine-induced B cell memory. When antibodies decline, memory B cells are expected to persist and perform their function, preventing clinical disease.

In-vivo visualization of the photoreceptors using Spectralis High Magnification Module imaging in central serous chorioretinopathy.

Purpose: To visualize photoreceptors using the Spectralis High Magnification Module (HMM) in a case of central serous chorioretinopathy (CSCR) and to correlate the findings with those of optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A).

Observations: A 35-year-old Caucasian male presenting with chronic CSCR in the left eye was examined using HMM, OCT and OCT-A. The photoreceptors mosaic was assessed both in diseased and apparently uninvolved areas.

The Nuts and Bolts of SARS-CoV-2 Spike Receptor-Binding Domain Heterologous Expression.

COVID-19 is a highly infectious disease caused by a newly emerged coronavirus (SARS-CoV-2) that has rapidly progressed into a pandemic. This unprecedent emergency has stressed the significance of developing effective therapeutics to fight the current and future outbreaks. The receptor-binding domain (RBD) of the SARS-CoV-2 surface Spike protein is the main target for vaccines and represents a helpful "tool" to produce neutralizing antibodies or diagnostic kits.

Kinetics of hydrocortisone sodium phosphate penetration into the human aqueous humor after topical application.

Aim Of The Study: Hydrocortisone is a soft steroid with low anti-inflammatory properties and a short duration of action, used to manage several ocular conditions. The clinical benefits and side effects associated with hydrocortisone are well documented, but its basic pharmacokinetic in the eye is yet to be fully elucidated. The purpose of this study is to investigate the anterior chamber penetration capabilities of hydrocortisone when used in different concentrations as eye drops treatment.

COVID-eVax, an electroporated DNA vaccine candidate encoding the SARS-CoV-2 RBD, elicits protective responses in animal models.

The COVID-19 pandemic caused by SARS-CoV-2 has made the development of safe and effective vaccines a critical priority. To date, four vaccines have been approved by European and American authorities for preventing COVID-19, but the development of additional vaccine platforms with improved supply and logistics profiles remains a pressing need. Here we report the preclinical evaluation of a novel COVID-19 vaccine candidate based on the electroporation of engineered, synthetic cDNA encoding a viral antigen in the skeletal muscle.

Real-world outcomes of anti-VEGF therapy in treatment-naïve neovascular age-related macular degeneration diagnosed on OCT angiography: the REVEAL study.

Purpose: To compare the 12 months visual and anatomical outcomes of treatment-naïve neovascular age-related macular degeneration (nAMD) patients diagnosed by optical coherence tomography angiography (OCT-A) compared with fluorescein angiography (FA)/indocyanine green angiography (ICGA), after anti-VEGF treatment in a real-world setting.

Methods: Monocentric, observational, parallel-group study of nAMD patients diagnosed with either FA/ICGA or non-invasive OCT-A methods. Patients were treated with a fixed dosing regimen of intravitreal ranibizumab or aflibercept and followed up for 12 months.

Comparison of two different scleral fixation techniques of posterior chamber Carlevale lens.

To investigate the surgical outcomes of 2 different scleral fixation techniques of the new single-piece foldable acrylic Carlevale lens (Soleko) and to compare our results with previous reports of the literature.A retrospective, non-randomized comparative study involving 2 series of patients who underwent 2 different scleral fixation techniques of Carlevale lens was performed. Minimum follow-up of 3 months was requested for inclusion in the study.

Photodynamic therapy as a treatment option for peripapillary pachychoroid syndrome: a pilot study.

Background: To investigate the anatomical and functional results in eyes with peripapillary pachychoroid syndrome (PPS) undergoing photodynamic therapy (PDT).

Methods: A total of 25 eyes from 23 patients with PPS treated with PDT were retrospectively evaluated in this multicentric study. Main outcome measure was the proportion of eyes that achieved treatment success, defined as a decrease in both subretinal fluid (SRF) height and central subfield thickness (CST), at 3 months after PDT compared to baseline.

A novel approach for scleral fixation using Carlevale lens.

Purpose: To evaluate the surgical outcomes and feasibility of a novel approach for scleral-fixation using a single-piece acrylic foldable Carlevale lens (Soleko).

Methods: Eighteen eyes of 18 patients with aphakia, dislocated IOL, subluxated lens, anisometropia, perforated trauma, and retinal detachment who underwent IOL implantation with a Carlevale lens were evaluated. All the patients underwent a standard ophthalmologic examination.

OCT-Angiography as a reliable prognostic tool in laser-treated proliferative diabetic retinopathy: The RENOCTA Study.

Purpose: To quantitatively assess retinal neovascularizations (RNVs) in proliferative diabetic retinopathy (PDR) before and after photocoagulative laser treatment (PLT) using Optical Coherence Tomography Angiography (OCT-A).

Methods: Consecutive patients with PDR were examined with fluorescein angiography (FA) and OCT-A before and after PLT. Baseline and after-treatment FA images were quantitatively analyzed to assess both the RNVs area and leakage area.

The role of ozonized oil and a combination of tobramycin/dexamethasone eye drops in the treatment of viral conjunctivitis: a randomized clinical trial.

Purpose: To determine whether topical tobramycin 0.3%/dexamethasone 0.1% plus ozonized oil eye drops reduces clinical signs and infectious viral titers of presumed viral conjunctivitis more than tobramycin/dexamethasone eye drops alone.

A new water soluble MAPK activator exerts antitumor activity in melanoma cells resistant to the BRAF inhibitor vemurafenib.

Recovery of mitogen activated protein kinase (MAPK) or activation of alternative pathways, such as the PI3K/AKT/mTOR, are involved in acquired resistance to BRAF inhibitors which represent the first-line treatment of BRAF-mutated metastatic melanoma. We recently demonstrated that 6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol (NBDHEX) and its water soluble analog 2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)ethoxy)ethoxy)ethanol (MC3181) trigger apoptosis in BRAF V600E mutated melanoma cells through activation of the MAPK c-Jun N-terminal kinase (JNK). Herein, we investigated whether NBDHEX and MC3181 might exert antitumor activity against BRAF V600E mutated human melanoma cells rendered resistant to the BRAF inhibitor vemurafenib.

Mutations of human DNA topoisomerase I at poly(ADP-ribose) binding sites: modulation of camptothecin activity by ADP-ribose polymers.

Background: DNA topoisomerases are key enzymes that modulate the topological state of DNA through the breaking and rejoining of DNA strands. Human topoisomerase I belongs to the family of poly(ADP-ribose)-binding proteins and is the target of camptothecin derived anticancer drugs. Poly(ADP-ribosyl)ation occurs at specific sites of the enzyme inhibiting the cleavage and enhancing the religation steps during the catalytic cycle.

Pharmacological inhibition of poly(ADP-ribose) polymerase-1 modulates resistance of human glioblastoma stem cells to temozolomide.

Background: Chemoresistance of glioblastoma multiforme (GBM) has been attributed to the presence within the tumor of cancer stem cells (GSCs). The standard therapy for GBM consists of surgery followed by radiotherapy and the chemotherapeutic agent temozolomide (TMZ). However, TMZ efficacy is limited by O6-methylguanine-DNA-methyltransferase (MGMT) and Mismatch Repair (MMR) functions.

PARP-1 modulates amyloid beta peptide-induced neuronal damage.

Amyloid beta peptide (Aβ) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with Aβ25-35 fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. Aβ25-35 induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050.

Glucocorticoid-induced tumor necrosis factor receptor family-related ligand triggering upregulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and promotes leukocyte adhesion.

The interaction of glucocorticoid-induced tumor necrosis factor receptor-family related (GITR) protein with its ligand (GITRL) modulates different functions, including immune/inflammatory response. These effects are consequent to intracellular signals activated by both GITR and GITRL. Previous results have suggested that lack of GITR expression in GITR(-/-) mice decreases the number of leukocytes within inflamed tissues.

Epilepsy and brain injury: a case report of a dramatic neuropsychiatric vicious circle.

Primary Objective: Early treatment of epilepsy is warranted to avoid possible severe consequences. This study aimed to assess the value of treatment in a patient who developed epilepsy after major brain surgery.

Design: Case description.

Influence of MLH1 on colon cancer sensitivity to poly(ADP-ribose) polymerase inhibitor combined with irinotecan.

Poly(ADP-ribose) polymerase inhibitors (PARPi) are currently evaluated in clinical trials in combination with topoisomerase I (Top1) inhibitors against a variety of cancers, including colon carcinoma. Since the mismatch repair component MLH1 is defective in 10-15% of colorectal cancers we have investigated whether MLH1 affects response to the Top1 inhibitor irinotecan, alone or in combination with PARPi. To this end, the colon cancer cell lines HCT116, carrying MLH1 mutations on chromosome 3 and HCT116 in which the wild-type MLH1 gene was replaced via chromosomal transfer (HCT116+3) or by transfection of the corresponding MLH1 cDNA (HCT116 1-2) were used.

MSH3 expression does not influence the sensitivity of colon cancer HCT116 cell line to oxaliplatin and poly(ADP-ribose) polymerase (PARP) inhibitor as monotherapy or in combination.

Purpose: Defective expression of the mismatch repair protein MSH3 is frequently detected in colon cancer, and down-regulation of its expression was found to decrease sensitivity to platinum compounds or poly(ADP-ribose) polymerase inhibitors (PARPi) monotherapy. We have investigated whether MSH3 transfection in MSH3-deficient colon cancer cells confers resistance to oxaliplatin or PARPi and whether their combination restores chemosensitivity.

Methods: MSH3-deficient/MLH1-proficient colon cancer HCT116(MLH1) cells were transfected with the MSH3 cDNA cloned into the pcDNA3.