Science: Y10 Biology and Environmental Science

The aim of this multicentre, randomised,
controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes.

Clinical studies on the treatment of type 1 diabetes with device-encapsulated pancreatic precursor cells derived from human embryonic stem cells found that insulin output was insufficient for clinical benefit.

In this 1-year, multicenter, randomised, controlled trial, we compared the efficacy of sensor-augmented pump therapy (pump therapy) with that of a regimen of multiple daily insulin injections (injection therapy) in 485 patients (329 adults and 156 children) with inadequately controlled type 1 diabetes.

The benefit of initiation of insulin pump therapy (continuous subcutaneous insulin infusion; CSII) in patients with type 1 diabetes using continuous glucose monitoring (CGM) has not been studied. We aimed to assess glycaemic outcomes when switching from multiple daily injections (MDI) to CSII in adults with type 1 diabetes using CGM.

The scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Transplantation of encapsulated stem cell-derived islets (SC islets) might extend the applicability of islet transplantation to a larger cohort of patients.

Type 1 diabetes results from the destruction of insulin-producing pancreatic b-cells by T cell-mediated autoimmune responses1. Exogenous insulin is used for the control of blood glucose in diabetic patients; however, hypoglycaemic episodes are unavoidable. Over the last several decades, islet transplantation has been developed as a promising method to achieve strict control of blood glucose and a potential cure for type 1 diabetes.

Many biotechnological innovations have shaped the contemporary healthcare system with significant progress to treat or cure several acute conditions and diseases of known causes (particularly infectious, trauma). Some have been successful while others have created additional health care challenges.

Many forecasts during the past 30 years have anticipated amazing advances in biotech—including cures for disease, eradication of hunger, and the means to transition away from petrochemical dependence—but the story of biotech has been one of incremental gains in food and material production, and medical advances. During the next 20 years, however, biotech is likely to transform a broader range of human experiences.

Strategic plan for health and medicine

There is a strong rationale to consider future cell therapeutic approaches for cystic fibrosis (CF) in which autologous proximal airway basal stem cells, corrected for CFTR mutations, are transplanted into the patient’s lungs. We assessed the possibility of editing the CFTR locus in these cells using zinc-finger nucleases and have pursued two approaches.

Survival among people with cystic fibrosis (CF) has increased worldwide over the past three decades. In countries where patients have access to specialised CF centres, the number of people with CF aged 18
years or over now equals or even exceeds that of the paediatric population. Before 1970, many individuals with CF died in infancy and, globally, the median age at death was only 8 years. However, with the introduction
of multidisciplinary care teams and specialised CF centres, survival around the world began to improve.

The autosomal recessive disease cystic fibrosis (CF) was once untreatable and deadly in childhood, but now most patients survive to adulthood. Many countries have instituted CF newborn screening because early diagnosis improves outcome.

Cystic fibrosis (CF) is a monogenic disorder caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Mortality in CF patients is mostly due to respiratory sequelae. Challenges with gene delivery have limited attempts to treat CF using in vivo gene therapy, and low correction levels have hindered ex vivo gene therapy efforts.

Cystic fibrosis is a life-threatening disease that affects at least 100,000 people worldwide.
It is caused by a defect in the cystic fibrosis transmembrane regulator (CFTR) gene and presently, 360 CFTR-causing mutations have been identified. Since the discovery of the CFTR gene, the expectation of developing treatments that can substantially increase the quality of life or even cure cystic fibrosis patients is growing.

Although many efforts in cancer prevention and control have routinely focused on behavioural risk factors, such as tobacco use, or on the early detection of cancer, such as colorectal cancer screening, advances in genetic testing have created new opportunities for cancer prevention through evaluation of family history and identification of cancer-causing inherited mutations. Through the collection and evaluation of a family cancer history by a trained health care provider, patients and families at increased risk for a hereditary cancer syndrome can be identified, referred for genetic counselling and testing, and make informed decisions about options for cancer risk reduction.

Relatively little research has been conducted on female breast cancer in African American women.
Data from the Black Women's Health Study, a
prospective cohort study of African American women, were used to assess breast cancer risk in relation to family history of cancer. Since 1995, participants have completed biennial postal questionnaires on health status, risk factors,
and family history of cancer.

Population breast cancer screening programs
by mammography are offered to women based on age. It has been suggested that a screening program based on genetic risk profile could be more effective by targeting interventions at those at higher genetic risk. This study explores women’s attitudes towards genetic testing for breast cancer susceptibility in order to target breast cancer prevention.

In the Ashkenazi Jewish (Ai) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2.

This manuscript details an investigation into the potential of mass spectrometry based serum biomarker discovery for differentiating between early and late-stage breast cancer patients. The study employs a ‘feature-first’ approach, focusing on MS1 scan spectra differences and applies both traditional and computational methods to analyse these differences.

Breast cancer stem-like cells (CSC) are an important therapeutic target as they are predicted to be responsible for tumor initiation, maintenance, and metastases. Interleukin (IL)-8 is upregulated in breast cancer and is associated with poor prognosis. Breast cancer cell line studies indicate that IL-8 via its cognate receptors, CXCR1 and CXCR2, is important in regulating breast CSC activity. We investigated the role of IL-8 in the regulation of CSC activity using patient-derived breast cancers and determined the potential benefit of combining CXCR1/2 inhibition with HER2-targeted therapy.

During breast cancer recurrence, drug therapy is planned based on the biological characteristics of the primary tumor. However, the mechanisms underlying these changes have not yet been clarified. A 59-year-old woman underwent breast cancer surgery 23 years
previously and received postoperative hormone therapy for 2 years.

This study assessed the influence of age, co-morbidity and frailty on 5-year survival outcomes after breast conservation surgery (BCS) with radiotherapy (RT) versus mastectomy (with or without RT) in women with early invasive breast cancer.

Breast cancer remains a primary global health concern due to its limited treatment options, frequent disease recurrence, and high rates of morbidity and mortality. Thereby, there is a need for more effective treatment approaches. The proposal suggests that the combination of targeted therapy with other antitumoral agents could potentially address drug resistance. In this study, we examined the antitumoral effect of combining metformin, an antidiabetic drug, with targeted therapies, including tamoxifen for estrogen receptor‑positive (MCF7), trastuzumab for HER2‑positive (SKBR‑3), and antibody against ROR1 receptor for triple‑negative breast cancer (MDA‑MB‑231).

Metformin, the most widely prescribed drug for treatment of type 2 diabetes, has been shown to exert significant anticancer effects. Hyperthermia has been known to kill cancer cells and enhance the efficacy of various anti-cancer drugs and radiotherapy. We investigated the combined effects of metformin and hyperthermia against MCF-7 and MDA-MB-231 human breast cancer cell, and MIA PaCa-2 human pancreatic cancer cells. Incubation of breast cancer cells with 0.5–10 mM metformin for 48 h caused significant clonogenic cell death.

Gene therapies aim to deliver a therapeutic payload to specified tissues with underlying protein deficiency. Since the 1990s, gene
therapies have been explored as potential treatments for chronic conditions requiring lifetime care and medical management.

During the previous decade, there has been significant progress in the field of gene therapy. Much of this has been fueled by the successful application of adeno-associated virus (AAV) as a gene transfer vector. Despite this progress, critical challenges to the application of AAV in gene therapy persist, namely a significantly limited transgene capacity, immunotoxicity, and hepatotoxicity, as well as the cost of
production and standardization of these novel biologics.

Stargardt disease (STGD) is the most common form of inherited juvenile macular dystrophy and is caused by sequence variants in the ABCA4 gene. Due to its genetic complexity and phenotypic variability, STGD poses significant therapeutic challenges. In the past decade, a lot of progress has been made regarding our understanding of the molecular and clinical aspects of STGD, along with its mechanisms. This has led to the development of new therapies, and there are human clinical trials currently ongoing. This paper evaluates the emergence of pharmacological approaches targeting the visual cycle to mitigate retinal damage, the role of gene therapy in correcting specific genetic defects, and the use of stem cell therapies aimed at retinal regeneration by showcasing the latest clinical trials and precision medicine approaches.

Stargardt disease (STGD) is an autosomal recessive retinal dis-order caused by a monogenic ABCA4 mutation. Currently, there is no effective therapy to cure Stargardt disease. The replacement of mutated ABCA4 with a functional gene remains an attractive strategy.

Stargardt disease (STGD) is the most common form of inherited retinal genetic disorders and is often caused by mutations in ABCA4. Gene therapy has the promise to effectively treat monogenic retinal disorders.

Embryonic stem cells hold great promise for various diseases because of their unlimited capacity for self-renewal and ability to differentiate into any cell type in the body. However, despite over 3 decades of research, there have been no reports on the safety and potential efficacy of pluripotent stem cell progeny in Asian patients with any disease.

Inherited retinal dystrophies, including Stargardt disease, are a group of genetic eye dis-
eases that currently lack effective treatment options. The CRISPR-Cas9 gene editing system and human induced pluripotent stem cells (hiPSCs) offer a promising avenue for treating Stargardt disease, a devastating genetic eye disorder.

A variety of genetic cardiovascular diseases may one day be curable using gene editing technology. Germline genome editing and correction promises to permanently remove monogenic cardiovascular disorders from the offspring and subsequent generations of affected families.

Cardiovascular disease (CVD) is one of the biggest threats to public health worldwide.
Identifying key genetic contributors to CVD enables clinicians to assess the most effective treatment course and prognosis, as well as potentially inform family members. This often involves either whole exome sequencing (WES) or targeted panel analysis of known pathogenic genes. In the future, tailored or personalised therapeutic strategies may be implemented, such as gene therapy.

Research on mechanisms underlying monogenic cardiac diseases such as primary arrhythmias and cardiomyopathies has until recently been hampered by inherent limitations of heterologous cell systems, where mutant genes are expressed in non cardiac cells, and physiological differences between humans and experimental animals.

Over the past 2 decades, investigators in the field of cardiac genetics have evolved a complex understanding of the pathophysiological basis of inherited cardiac diseases, which predispose individuals to sudden cardiac death.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy worldwide, affecting approximately 1 in 500 individuals. Current therapeutic interventions include lifestyle optimisation, medications, septal reduction therapies, and, rarely, cardiac transplantation. Advances in our understanding of disease-causing genetic variants in HCM and their associated molecular mechanisms have led to the potential for targeted therapeutics and implementation of precision and personalised medicine.

Dominant missense pathogenic variants in cardiac myosin heavy chain cause hypertrophic cardiomyopathy (HCM), a currently incurable disorder that increases risk for stroke, heart failure and sudden cardiac death. In this study, we assessed two different genetic therapies—an adenine base editor (ABE8e) and a potent Cas9 nuclease delivered by AAV9—to prevent disease in mice carrying the heterozygous HCM pathogenic variant myosin R403Q.

CRISPR-Cas9 gene editing is emerging as a prospective therapy for genomic mutations. However, current editing approaches are directed primarily toward relatively small cohorts of patients with specific mutations. Here, we describe a cardioprotective strategy potentially applicable to a broad range of patients with heart disease.

Cell therapy can improve cardiac function in animals and humans after injury, but the mechanism is unclear. We performed cell therapy experiments in genetically engineered mice that permanently express green fluorescent protein (GFP) only in cardiomyocytes after a pulse of 4-OH-tamoxifen.