Cell and Tissue Journal

Abstract Introduction: Heat stress is one of the most significant environmental stresses that limits the growth, metabolism, and productivity of crops worldwide. As global temperatures rise due to climate change, the intensity and frequency of hot and dry days are increasing significantly. This phenomenon poses a serious threat to agricultural productivity, as the simultaneous occurrence of drought and heat stress adversely affects various agricultural characteristics. These include traits related to growth and development, biomass accumulation, and overall yield. In this context, various physiological traits such as leaf water content, canopy temperature, membrane stability, chlorophyll content, stomatal conductance, chlorophyll fluorescence, and photosynthesis are seriously disrupted. Understanding these impacts is crucial for developing effective strategies to mitigate heat stress and enhance crop resilience.
The objective of this article is to investigate the effects, mechanisms of tolerance, management, and control of heat stress in crop plants. This article is prepared as a review of the literature and examines various strategies for coping with heat stress in plants. This article is a review article that was obtained by searching related articles in reliable sites (Google Scholar, Web of Science, PubMed, Scopus, and SID) and aims to investigate the effects, mechanisms of tolerance, management, and control of heat stress. Plants have developed a range of adaptive defense strategies to cope with heat stress. These strategies include mechanisms for removing reactive oxygen species (ROS), producing osmolytes, and modulating secondary metabolites and various hormones. The survival of the plant under heat stress depends on its ability to perceive the stress, produce and transmit signals, and initiate appropriate physiological and biochemical changes. For instance, changes in gene expression and metabolite synthesis significantly improve plant tolerance to heat stress. Adaptation mechanisms to heat stress include leaf curling, which reduces water loss, precocity, which allows for earlier maturation, and the accumulation of osmotic protectors that help maintain cellular integrity. Additionally, the activation of antioxidant defense mechanisms plays a crucial role in mitigating oxidative damage caused by heat stress. Heat stress can be effectively mitigated through various agricultural practices. These practices include selecting appropriate planting methods, choosing the right planting date, selecting suitable cultivars that are more resilient to heat, and implementing effective irrigation methods. Furthermore, the exogenous use of protectants, such as osmotic protectors (e.g., proline, glycine betaine, trehalose), phytohormones (e.g., abscisic acid, gibberellic acids, jasmonic acids), signaling molecules (e.g., nitric oxide), polyamines (e.g., putrescine, spermidine, spermine), trace elements (e.g., selenium, silicon), and essential nutrients (e.g., nitrogen, phosphorus, potassium, calcium) are effective in reducing the damage caused by heat stress. These practices not only enhance plant resilience but also contribute to maintaining agricultural productivity under changing climatic conditions.
Conclusion: Molecular and biotechnological strategies are also crucial for developing heat stress tolerance in plants. Advances in molecular biology have facilitated a better understanding of the mechanisms underlying heat stress tolerance. Plants respond to environmental stresses by modulating the expression of multiple genes and coordinating gene expression in various ways. The expression of heat shock proteins (HSPs) plays a vital role in protecting intracellular proteins from denaturation, thereby maintaining their stability and function. By integrating molecular approaches with traditional breeding techniques, researchers can develop crop varieties that are better equipped to withstand heat stress. Overall, a comprehensive understanding of heat stress mechanisms and effective management strategies is essential for ensuring sustainable agricultural productivity in the face of climate change.

Abstract Introduction: Global climate change has significantly increased the frequency and intensity of abiotic stresses, thereby limiting plant growth, development, and overall yield by damaging physiological systems. In response to environmental stressors, plants have evolved various adaptive mechanisms, including the accumulation of compatible solutes such as glycine betaine (GB), which plays a pivotal role in protecting cellular functions under adverse conditions. Also known simply as betaine, this compound is a methylated glycine derivative recognized across plant species for its ability to mitigate the deleterious effects of stressful environments. Its zwitterionic structure; comprising a positively charged trimethylammonium group and a negatively charged carboxyl group, confers high solubility and chemical stability to the molecule.
Owing to its excellent biocompatibility, favorable carbon-to-nitrogen ratio, and high-concentration accumulation, glycine betaine can enhance plant tolerance against a wide spectrum of abiotic stresses. Specifically, GB contributes to photosynthetic recovery and the alleviation of oxidative stress by reducing the accumulation and facilitating the detoxification of reactive oxygen species (ROS). Furthermore, it plays a crucial role in stabilizing membranes and macromolecules, while protecting key components of the photosynthetic apparatus, such as the Rubisco enzyme, Photosystem II (PSII), quaternary enzymes, and complex protein structures. Notably, glycine betaine can accumulate at high concentrations within plant cells without interfering with normal metabolic processes, thereby significantly increasing resilience to various osmotic stresses, extreme temperatures (heat and cold), and oxidative damage. The biosynthesis of glycine betaine occurs through distinct metabolic pathways, including the choline oxidation pathway (prevalent in plants and mammals), the direct glycine methylation pathway (specific to certain bacteria and halophytes), the choline dehydrogenase pathway, and the serine metabolism pathway. Such diversity underscores the vital importance of this osmolyte in mediating responses to environmental stresses. Recently, biotechnological interventions, such as Agrobacterium-mediated transformation, have successfully enhanced stress tolerance in susceptible species by overexpressing key genes, most notably codA, BADH, GSMT, and SDMT. Given the functional diversity of genes involved in the glycine betaine biosynthetic pathway, extensive efforts have been made to develop transgenic plants capable of effective accumulation of this metabolite; however, serious challenges such as unstable and weak transgene expression remain as key obstacles in this path. Factors including promoter type, genomic integration site, and epigenetic factors can influence the final performance. Furthermore, the overexpression of enzymes in the glycine betaine biosynthetic pathway may potentially impair growth by disrupting metabolic stability. Therefore, future research should focus on decoding the molecular networks regulating the biosynthesis, signaling, and transport of glycine betaine, particularly its crosstalk with phytohormones, transcription factors, and the identification of stress-inducible promoters. Additionally, optimizing transformation protocols and synchronizing glycine betaine gene expression with the overall plant metabolism are essential.
Aims: This review examines the biosynthesis, physiological functions, and molecular regulation of glycine betaine (GB). It highlights genetic engineering techniques to boost GB production, offering sustainable strategies for enhancing crop tolerance to environmental stresses.
Conclusion: In-planta biosynthesis of glycine betaine (GB) offers a more sustainable alternative to exogenous application, aligning closely with the principles of green agriculture. By integrating GB synthesis pathways, genetically engineered crops can autonomously boost metabolite production and bolster stress resilience, thereby eliminating the logistical costs of external treatments. Furthermore, a more profound investigation into these biosynthetic pathways will facilitate the identification and cloning of novel target genes, ultimately maximizing GB accumulation and enhancing environmental tolerance.

Abstract Bladder cancer is one of the most common malignancies of the urinary tract and ‎originates from the bladder epithelium. Despite advances in surgery, chemotherapy, ‎radiation, and immunotherapy, bladder cancer remains a major clinical challenge ‎because of its high recurrence rate, risk of progression, and the need for long-term ‎surveillance and repeated interventions. In recent years, vaccine-based immunotherapy ‎has gained increasing attention as a promising strategy for improving antitumor ‎immune responses, reducing relapse, and enhancing therapeutic outcomes across ‎different disease stages.‎
Bacillus Calmette–Guérin (BCG) is the first and most established vaccine used in ‎bladder cancer treatment and remains the standard intravesical adjuvant ‎immunotherapy for non muscle invasive bladder cancer (NMIBC). Its antitumor ‎activity is largely mediated by immunomodulatory effects within the bladder ‎microenvironment, including activation of innate immune cells, induction of ‎pro inflammatory cytokines, and subsequent priming of adaptive immune responses ‎that support cytotoxic T cell–mediated tumor control. However, a substantial ‎proportion of patients experience intolerance, inadequate response, recurrence, or ‎resistance, underscoring the need for next generation vaccine strategies with improved ‎specificity and durability.‎
Accordingly, several emerging vaccine platforms have been investigated. Cell based ‎vaccines, particularly dendritic cell (DC) vaccines, aim to exploit the antigen presenting ‎function of DCs to enhance tumor specific T cell activation using tumor lysates, ‎defined tumor associated antigens, or engineered immunostimulatory constructs. In ‎parallel, monoclonal antibody–based approaches that target tumor associated antigens ‎have been explored as immunotherapeutic tools that may complement vaccine-‎induced immunity. Peptide vaccines provide a more defined strategy by stimulating ‎antigen specific responses against selected epitopes, and their performance may be ‎strengthened through the use of appropriate adjuvants, optimized epitope selection, ‎and improved delivery systems. More recently, mRNA vaccines have attracted ‎considerable interest because they enable rapid and flexible design, can encode one or ‎multiple tumor antigens, and may induce robust cellular immunity. These platforms ‎also offer opportunities for personalization based on patient specific antigenic profiles ‎and may be manufactured in a scalable manner.‎
Combination therapy is an important direction in this field. Pairing vaccine approaches ‎with immune checkpoint inhibitors (e.g., PD 1/PD L1 blockade) may enhance ‎therapeutic efficacy by reversing tumor mediated immune suppression and improving ‎the magnitude and durability of antitumor responses. In addition, integrating vaccines ‎with conventional modalities such as chemotherapy or radiotherapy may further ‎augment immunogenicity through increased antigen release, activation of danger ‎signaling pathways, and immune priming, thereby potentially converting ‎immunologically “cold” tumors into more responsive disease states.‎
This review summarizes major vaccine strategies investigated for bladder cancer, ‎including BCG, cell based vaccines, peptide vaccines, and mRNA vaccines, and ‎discusses their proposed mechanisms, advantages, and current limitations. Despite ‎encouraging progress, key challenges remain, including tumor heterogeneity, antigen ‎loss, immune evasion, optimization of delivery and dosing schedules, manufacturing ‎complexity, and cost. Future research should focus on refining antigen discovery and ‎vaccine design, identifying predictive biomarkers for patient selection and response ‎monitoring, optimizing combination regimens to maximize synergy, and conducting ‎larger, well designed clinical studies to support clinical translation. Overall, vaccine-‎based immunotherapy represents a rapidly evolving and promising avenue that may ‎contribute to more effective, durable, and individualized treatment of bladder cancer ‎for patients across disease stages.‎