Osteoarthritis represents a huge socioeconomic burden and has a significant impact on daily life and productivity. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the management of osteoarthritis to curb inflammation, pain, and stiffness and improve physical function. However, due to the various side effects, most healthcare professionals avoid using NSAIDs for a long period. Nonselective cyclooxygenase (COX) inhibitors and cyclooxygenase-1 (COX-1) inhibitors are associated with increased gastrointestinal adverse effects due to the inhibition of prostaglandins, which are responsible for protecting the gastric mucosa. Cyclooxygenase-2 (COX-2) inhibitors are associated with an increased incidence of adverse cardiovascular effects due to their COX-2 inhibitory activity in the circulatory system. Therefore, there is a need for a newer NSAID that has a better safety profile to be used in osteoarthritis. Polmacoxib is a new, orally active, first-in-class NSAID that is a dual inhibitor of COX-2 and carbonic anhydrase (CA). The dual mode of action exhibited by polmacoxib is expected to minimize adverse cardiovascular effects while achieving maximum effectiveness in inflamed osteoarthritic joints. This article aims to review the pharmacological properties, clinical efficacy, and safety data of polmacoxib in osteoarthritis.

Sulfonamides have gained prominence as versatile agents in cancer therapy, effectively targeting a spectrum of cancer-associated enzymes. This review provides an extensive exploration of their multifaceted roles in cancer biology. Sulfonamides exhibit adaptability by acting as tyrosine kinase inhibitors, disrupting pivotal signaling pathways in cancer progression. Moreover, they disrupt pH regulation mechanisms in cancer cells as carbonic anhydrase inhibitors, inhibiting growth, and survival. Sulfonamides also serve as aromatase inhibitors, interfering with estrogen synthesis in hormone-driven cancers. Inhibition of matrix metalloproteinases presents an opportunity to impede cancer cell invasion and metastasis. Additionally, their emerging role as histone deacetylase inhibitors offers promising prospects in epigenetic-based cancer therapies. These diverse roles underscore sulfonamides as invaluable tools for innovative anti-cancer treatments, warranting further exploration for enhanced clinical applications and patient outcomes.

UNASSIGNED: Macular edema (ME) is a vision-threatening condition that commonly develops as a consequence of ocular diseases, including age-related macular degeneration, retinal vaso-occlusion of the central retinal vein and its branches, diabetic retinopathy, central serous chorioretinopathy, uveitis, retinitis pigmentosa, pseudophakia, ocular trauma, and drug toxicity. The treatment of ME remains challenging, although steroids and vascular endothelial growth factor inhibitors are available. Cost-effective therapy using a noninvasive administration route is required. This study aimed at reviewing the role of carbonic anhydrase inhibitors (CAIs) in the management of ME.
UNASSIGNED: A literature search was conducted using PubMed/MEDLINE and Google Scholar for studies from January 2000 to March 2022. The following keywords were used in various combinations: \"macular edema\", \"carbonic anhydrase\", \"carbonic anhydrase inhibitors\", \"acetazolamide\", \"dorzolamide\", and \"brinzolamide\".
UNASSIGNED: Articles with high or medium clinical relevance were selected for this review. We found that multiple studies have demonstrated the relevance and efficacy rates of CAIs in the management of ME. Most published studies focused on acetazolamide and dorzolamide, with nearly all studies reporting therapeutic responses.
UNASSIGNED: ME is the leading cause of vision loss and requires noninvasive and cost-effective pharmacotherapy. With progress in the understanding of ME, particularly the role of carbonic anhydrase as a key driver, CAIs are the focus of research. Further optimization of the choice of CAIs and retinal bioavailability, potentially with nanoparticle formulations, is required to enable the effective management of ME. Further research is warranted to address the therapeutic effects of CAIs in different formulations.

Metabolic alkalosis is a common acid-base imbalance frequently observed in intensive care unit (ICU) patients and is associated with increased mortality. Post-hypercarbia alkalosis (PHA) is a type of metabolic alkalosis caused by sustained high serum bicarbonate levels following a rapid resolution of hypoventilation in patients with chronic hypercapnia due to prolonged respiratory disturbance. Common causes of chronic hypercapnia include chronic obstructive pulmonary disease (COPD), central nervous system disorders, neuromuscular disorders, and narcotic abuse. Rapid correction of hypercapnia through hyperventilation leads to a swift normalization of pCO2, which lacks renal compensation, consequently causing an increase in plasma HCO3- levels and severe metabolic alkalosis. Most of PHA occurs in the ICU setting requiring mechanical ventilation and can progress severe alkalemia due to secondary mineralocorticoid excess from volume depletion or decreased HCO3- excretion from decreased glomerular filtration rate and increased proximal tubular reabsorption. PHA is associated with increased ICU stay, ventilator dependency, and mortality. Acetazolamide, a carbonic anhydrase inhibitor, has been utilized for managing PHA by inducing alkaline diuresis and reducing tubular reabsorption of bicarbonate. While acetazolamide effectively improves alkalemia, its impact on hard outcomes may be limited by factors such as patient complexity, co-administered medications, and underlying conditions contributing to alkalosis.

Malaria is a public health problem that causes thousands of deaths, primarily in children in African regions. Artemisinin-based combination therapies (ACTs) have helped to save thousands of lives; however, due to Plasmodium\'s resistance to available treatments, there is a need to search for new low-cost drugs that act through different mechanisms of action to contain this disease. This review shows that compounds with sulfonamide moiety, possibly, act as inhibitors of P. falciparum carbonic anhydrases, moreover, when linked to a variety of heterocycles potentiate the activities of these compounds and may be used in the design of new antimalarial drugs.

Biocatalytic conversion of greenhouse gases such as carbon dioxide into commercial products is one of the promising key approaches to solve the problem of climate change. Microbial enzymes, including carbonic anhydrase, NAD-dependent formate dehydrogenase, ribulose bisphosphate carboxylase, and methane monooxygenase, have been exploited to convert atmospheric gases into industrial products. Carbonic anhydrases are Zn2+-dependent metalloenzymes that catalyze the reversible conversion of CO2 into bicarbonate. They are widespread in bacteria, algae, plants, and higher organisms. In higher organisms, they regulate the physiological pH and contribute to CO2 transport in the blood. In plants, algae, and photosynthetic bacteria carbonic anhydrases are involved in photosynthesis. Converting CO2 into bicarbonate by carbonic anhydrases can solidify gaseous CO2, thereby reducing global warming due to the burning of fossil fuels. This review discusses the three-dimensional structures of carbonic anhydrases, their physiological role in marine life, their catalytic mechanism, the types of inhibitors, and their medicine and industry applications.

Targeted inhibition of misregulated protein-protein interactions (PPIs) has been a promising area of investigation in drug discovery and development for human diseases. However, many constraints remain, including shallow binding surfaces and dynamic conformation changes upon interaction. A particularly challenging aspect is the undesirable off-target effects caused by inherent structural similarity among the protein families. To tackle this problem, phage display has been used to engineer PPIs for high-specificity binders with improved binding affinity and greatly reduced undesirable interactions with closely related proteins. Although general steps of phage display are standardized, library design is highly variable depending on experimental contexts. Here in this review, we examined recent advances in the structure-based combinatorial library design and the advantages and limitations of different approaches. The strategies described here can be explored for other protein-protein interactions and aid in designing new libraries or improving on previous libraries.

The isoetid life-form was originally defined on morphological grounds; subsequent physiological investigations showed that all of the isoetids examined took up a large fraction of the inorganic C fixed in their leaves from the root medium under natural conditions, and that some of them carried out much of their assimilation of inorganic C via a CAM-like mechanism. Root-dominated uptake of inorganic C appeared to be unique to, and ubiquitous in, the isoetids. I However, a large capacity for CAM-like metabolism in submerged vascular plants is not universal in isoetids, nor is it restricted to this life-form, being also found in Crassulaa aquatica. The work described here shows that submerged specimens of the North American Eriocaulon decangulare have a high fraction of their dry weight in the root system, a trait characteristic of isoetids but uncommon in other submerged vascular plants. E. decangulare has vesicular-arbuscular mycorrhizas, as do other flowering plant isoetids hut not, generally, submerged Isoetes spp. Under conditions of natural supply of inorganic C, E. decangulare, like other isoetids, takes up most of its inorganic C through its roots. Uptake of inorganic C by both roots and shoots involves CO2 rather than HCO3 : photosynthesis at high external pH values does not exceed the rate of uncatalysed HCO3 - to CO2 conversion in the medium and there is no detectable extracellular carbonic anhydrase activity. Measurements of titratable acidity and of malate content of leaves sampled at dawn and at dusk showed that E. decangulare, growing and tested under either emersed or submersed conditions, did not exhibit CAM-like behaviour. CAM was also absent from three non-isoetid aquatic macrophytes (Amphibolic antarctica, Eeklonia radiata and Vallisneria spiralis) which were examined. E. decangulare thus resembles all other isoetids tested in acquiring much of its inorganic C via the root system. E. decangulare also resembles most of the isoetids which are not members of the Isoetaceae (e.g.) E. septangulare, Lobelia dortmanna and Subularia aquatica) but differs from submerged Isoetaceae and Littorella uniflora in lacking CAM. The ecological significance of uptake of CO2 via the roots and, where it occurs, of CAM in isoetids may be related to either inorganic C or, via improved N use efficiency, inorganic C as a limiting resource. The isoetid life-forms has evolved independently in at last five different families of vascular plants; it probably derived fairly immediately from terrestrial or amphibious ancestors with a similar rosette form. Emergent Isoetaceae with acquisition of CO2 via roots and CAM probably evolved from submerged isoetids. CONTENTS Summary 123 I. Introduction 126 II. Material and Methods 127 III. Results and Discussion 129 IV. Conclusions 142 Acknowledgements 142 References 143.

Carbonic anhydrase IX (CAIX) is a hypoxia-related protein considered as a predictor for oral squamous cell carcinoma (OSCC) biological behaviour. Nevertheless, this prognostic value is still yet to be validated. We aim to quantify prognostic significance of CAIX overexpression in OSCC by meta-analysis. We performed searches in MEDLINE, EMBASE, SCOPUS, WOS, WHO\'S databases, CPCI, and OATD from inception to August 2019. Overall survival (OS), disease-free survival (DFS), locoregional control (LC), and disease-specific survival (DSS) were considered as outcomes of interest. Overall 18 studies were included. CAIX overexpression was associated with worse OS (hazard ratio [HR] = 1.45 95% confidence interval [CI] 1.17-1.80) and DFS (HR = 1.98 95% CI 1.18-3.32). To the contrary, it was neither associated with LC (HR = 1.01 95% CI 0.50-2.02) nor with DSS (HR = 1.35 95% CI 0.78-2.33). Heterogeneity was negligible in all analyses except for DSS. Small studies effect was not significant for OS and DFS. This study shows that immunohistochemical CAIX assessment is a useful OSCC prognostic biomarker.

Introduction: Glaucoma affects more than 70 million people worldwide. One of the major therapeutic options for its management is based on the inhibition of the metalloenzyme carbonic anhydrases (CAs, EC 4.2.1.1). CA inhibitors (CAIs) diminish ocular hypertension in glaucomatous patients by reducing the rate of bicarbonate formation and thus, the secretion of the aqueous humor. Areas covered: This review is intended to cover the major contributions in terms of patent literature reports for the treatment of ophthalmic diseases by means of CAIs in a time frame spanning from 2013 to date. Expert opinion: The patent literature is dominated by innovative pharmaceutical formulations including a CAI alone or in combination with other therapeutic agents. Very few novelties within drug discovery are currently present and they mainly account for new CAI moieties and classical CAIs merged into scaffolds bearing additional chemical functionalities beneficial for the pharmacological treatment of the disease. It is reasonable to expect that in the near future the so-called \'old drugs\' will achieve pharmacological performances in the management of ocular hypertension beyond any expectations and thus open a new era of drug repurposing merely based on material science advancements.