Sher-e-Bangla Medical College

Electroporation, a widely used physical method for transiently increasing cell permeability, facilitates molecular delivery for therapeutic and research applications. While electroporation proves to be a useful process, the mechanisms of pore formation and molecular transport remain incompletely understood. This study investigates the dynamics of electropore formation in lipid bilayers using molecular dynamics (MD) simulations and subsequent molecular transport by quantitative diffusion modeling. MD simulations reveal different stages of pore formation under applied electric fields, focusing on the lipid headgroup realignment and the hydration process of the pores. An FDM (Finite Difference Method)-based transport model quantifies the transport of molecules, such as glucose, calcein and bleomycin, using pore dimensions obtained from MD simulations. The results demonstrate a size-dependent transport efficiency, with smaller molecules diffusing more rapidly than larger ones. This work underscores the synergy between atomistic simulations and macroscopic transport modeling. Also, the findings offer valuable insights for optimizing electroporation protocols and developing targeted delivery systems for drugs and genetic material.

The COVID-19 pandemic necessitated robust vaccination strategies, including booster doses to sustain immunity against SARS-CoV-2. The comparative immunogenicity of homologous (same vaccine type) versus heterologous (different vaccine types) booster regimens remains understudied, particularly in diverse settings. This study assesses anti-receptor binding domain (RBD) IgG antibody responses to these regimens in Bangladesh.

A prospective quasi-experimental study was conducted at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, from March 2022 to February 2023. Seventy-three participants, selected via convenience sampling, were grouped into homologous (n=40) or heterologous (n=33) vaccine regimens based on primary and booster vaccine types. Anti-RBD IgG levels were measured pre-booster and three weeks post-booster using the SARS-CoV-2 IgG II Quant Reagent Kit (Abbott, Ireland). Demographic and clinical factors (age, sex, BMI, diabetes, and blood pressure) were evaluated. Mann-Whitney U and Kruskal-Wallis tests were used, with p≤0.05 indicating significance.

Participants (mean age: 35.51 years, 79.5% male) showed higher pre-booster (median: 4499.65 vs. 1863.7 AU/mL, p<0.001) and post-booster (median: 13835.15 vs. 10423.3 AU/mL, p=0.014) anti-RBD IgG levels in the homologous group compared to the heterologous group. However, the heterologous group exhibited a greater fold increase (median: 4.6 vs. 3.65, p=0.024) of anti-RBD IgG levels. A higher proportion of participants in the homologous regimen achieved high post-booster IgG levels (>20,000 AU/mL, p=0.016). Diabetes significantly reduced antibody responses in the heterologous group (p=0.006). Hypertensive participants had significantly reduced antibody responses before (p=0.005) and after (p=0.001) the booster in the heterologous group and after (p=0.033) the booster in the homologous group. Age, sex, and BMI had no significant effect on the results.

Homologous regimens yield higher anti-RBD IgG levels, while heterologous regimens produce greater fold increases of anti-RBD IgG levels, indicating robust recall. Diabetes and hypertension impair responses, particularly in heterologous regimens. These findings support the need for tailored vaccination strategies to enhance immune protection.

Monogenetic disease alpha-1 antitrypsin deficiency (AATD) is the leading cause of emphysema, which is a major life-limiting chronic obstructive pulmonary disease (COPD). The current standard of care for severely affected individuals with lung disease is the periodic intravenous infusion of human AAT protein to restore circulating AAT levels to a protective level, known as augmentation therapy.  We did a systematic review to see the effect of gene therapy as a potential therapeutic option for AATD-related lung diseases. MEDLINE (via PubMed), SCOPUS, Web of Science, Cochrane Library, and EMBASE have been searched following PICO (Population, Intervention, Comparison, Outcome) criteria. After duplication removal, abstract and title screening, full-text screening was done by two individual reviewers. Then, the data were extracted, tabulated, and analyzed. A total of 1094 articles were found in the primary search. After a comprehensive review following strict inclusion and exclusion criteria, 14 articles have been included in the review. Evidence shows the response of gene therapy depends on multiple factors, e.g., what vector is used, route of therapy administration, duration of therapy, etc. The AAV8-CASI-luc vector, delivered intratracheally (IT), achieved sustained lung transgene expression for at least 52 weeks, but 29% of mice had persistent expression up to 72 weeks, providing therapeutic AAT protein levels, reducing experimental emphysema severity in mice. Intratracheal AAV8 in mice showed the highest AAT expression in the lung, outperforming AAV9, AAV5, AAV2, and AAV2 capsid mutants, providing long-term expression up to 4 months. Intrapleural administration of AAV5-hA1AT achieved higher lung and serum A1AT levels than intramuscular delivery, with AAV5 yielding 10 times higher levels than AAV2. Gene therapy using viral vectors has a potential role in producing AAT protein, which can be beneficial for AATD-related lung diseases. Human trials are necessary to establish the effectiveness and safety of gene therapy. In conclusion, while initial studies are encouraging, more research is needed to confirm the role of gene therapy.