The research team, led by scientists from Pondicherry University’s Andaman Campus, Nagasaki University, and Babasaheb Bhimrao Ambedkar Bihar University, systematically evaluated hundreds of studies to build the case that enzymes evolved under punishing marine conditions possess biochemical properties that terrestrial counterparts simply cannot replicate. Marine microbes thrive in salinities reaching five molar sodium chloride, temperatures spanning from subzero to above 100 degrees Celsius, and hydrostatic pressures exceeding 100 megapascals. These extremes have forged enzymes with exceptional thermostability, halotolerance, psychrophilicity, and catalytic efficiency, properties that translate directly into advantages for biomedical applications where conventional enzymes and drugs often fail.

The urgency of the search is underscored by sobering epidemiological data. A 2024 systematic analysis in The Lancet attributed 1.27 million direct deaths and 4.95 million associated deaths to bacterial antimicrobial resistance in 2019 alone, with forecasts projecting 1.91 million direct attributable deaths and 8.22 million associated deaths annually by 2050. Without accelerated intervention, the cumulative toll between 2025 and 2050 could reach 39 million deaths. Meanwhile, chronic inflammation quietly drives autoimmune disease, cardiovascular pathology, and neurodegeneration, while many existing cancer drugs suffer from off-target toxicity and eventual treatment resistance. The review positions marine enzymes as a fundamentally different therapeutic class capable of addressing all three challenges simultaneously.

In the inflammation arena, the standouts are superoxide dismutases, laccases, and chitinases. Superoxide dismutase catalyzes the dismutation of the superoxide anion into hydrogen peroxide and molecular oxygen, intercepting reactive oxygen species before they can generate the highly destructive peroxynitrite that damages lipids, proteins, and mitochondria. Marine versions, particularly the nickel-containing SOD found in cyanobacteria such as Prochlorococcus marinus, exhibit faster reaction rates and greater oxidative stress tolerance than conventional copper-zinc enzymes. In animal models of carrageenan-induced edema, marine SOD treatment reduced swelling, malondialdehyde levels, nitric oxide synthase activity, and leukocyte infiltration, while suppressing the master inflammatory transcription factor NF-κB and lowering secretion of the cytokines TNF-α, IL-1β, and IL-6. The commercially developed TetraSOD ingredient, derived from the microalga Tetraselmis chuii, demonstrated antioxidant and anti-inflammatory benefits in a rat model of metabolic syndrome, suggesting near-term applications in autoimmune, neuroinflammatory, and metabolic disorders.

Marine laccases, multicopper oxidases produced by fungi and bacteria in environments ranging from Antarctic waters to hypersaline lagoons, complement this antioxidant arsenal. Unlike peroxidases, which require hydrogen peroxide as a co-substrate and can become unstable during clinical use, laccases directly use molecular oxygen to oxidize phenolic inflammatory mediators. They also suppress NF-κB and MAPK signaling pathways in vitro, reducing IL-6 and TNF-α release. Chitinases add a third mechanism by hydrolyzing chitin into chitooligosaccharides that engage the pattern recognition receptors TLR9 and NOD2, triggering production of the anti-inflammatory cytokine IL-10. Recent work suggests the chitinase CHIT1 promotes microglial phagocytosis of amyloid plaques in models of Alzheimer’s disease, hinting at neuroprotective applications.

The oncology story is equally compelling, built on the principle of exploiting metabolic vulnerabilities unique to tumor cells. Marine-derived L-asparaginase, isolated from organisms including Bacillus tequilensis, Streptomyces species, and marine fungi, starves asparagine-dependent cancer cells by depleting extracellular L-asparagine, which activates p53-mediated apoptotic signaling and triggers mitochondrial outer membrane permeabilization, cytochrome c release, and caspase activation. One marine fungal asparaginase achieved an IC50 of 3.79 micrograms per milliliter against HCT-116, HepG2, and MCF-7 cancer cell lines, and importantly, marine variants show reduced glutaminase-associated toxicity and lower hypersensitivity potential compared with the Escherichia coli formulations currently used in leukemia therapy. Marine L-glutaminases from Halomonas meridiana and Halomonas aquamarina target glutamine-addicted colorectal tumors, with reported IC50 values of 7.0 and 13.2 micrograms per milliliter against LS 174 T and HCT-116 cells respectively, inducing endoplasmic reticulum stress and mitochondrial damage through cyclophilin A-caspase signaling.

Beyond nutrient starvation, marine enzymes attack tumors through oxidative and structural routes. Laccases from marine Streptomyces generate reactive oxygen species that preferentially damage tumor mitochondria, activating Bax, releasing cytochrome c, and downregulating the anti-apoptotic protein Bcl-2, while oxidase-inspired nanozyme systems have demonstrated ferroptosis-mediated tumor suppression with negligible systemic toxicity in preclinical models. Alkaline proteases from marine Streptomyces and Pseudoalteromonas species degrade collagen, fibronectin, and laminin in the tumor extracellular matrix, disrupting integrin signaling, softening stromal mechanics, and interfering with the invasive architecture that shields tumors from immune surveillance and drug penetration. Because tumor and normal tissues differ in nutrient dependence, redox balance, and matrix composition, these enzyme strategies achieve a degree of selectivity that conventional chemotherapy struggles to match.

The most dramatic results, however, may lie in the fight against antimicrobial resistance. Biofilms, the sticky extracellular polymeric fortresses that pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus construct to shield themselves from antibiotics and immune attack, are a leading cause of chronic, treatment-refractory infections. Marine alginate lyases from Flavobacterium, Sphingomonas, and Pseudoalteromonas carrageenovora specifically cleave the alginate strands of Pseudomonas biofilms, and when combined with the antibiotic ceftobiprole, achieved biofilm reductions of 60 to 69 percent, dramatically enhancing antibiotic penetration compared with antibiotic treatment alone. Serine and alkaline proteases bearing the catalytic Ser-His-Asp triad degrade bacterial surface proteins and biofilm matrix components, lowering minimum inhibitory concentrations of co-administered antibiotics, while marine chitinases breach fungal cell walls and affect Gram-positive bacteria. Collagenases and thiol proteases further destabilize established biofilms in models of persistent infection.

Yet the path from laboratory promise to clinical reality remains steep. Most marine enzymes evolved for conditions far from the human body’s 37 degrees Celsius and near-neutral pH, so protein engineering, PEGylation, and nanoparticle encapsulation are often needed to ensure physiological compatibility. The vast majority of ocean microbes cannot be cultured in the laboratory, a problem known as the great plate count anomaly, locking countless candidate enzymes within microbial dark matter, though metagenomics, single-cell genomics, and functional screening are now bypassing the need for cultivation. No pharmacokinetic profiles, immunogenicity assessments, or clinical trial data yet exist for these candidates, and regulatory pathways for marine-derived enzyme therapeutics remain underdeveloped. Directed evolution and recombinant expression systems have already demonstrated more than 100-fold improvements in catalytic efficiency for engineered protein systems, and artificial intelligence-guided discovery promises to accelerate identification of optimal candidates.

The review’s authors argue that the coming decade offers a transformational window if researchers prioritize preclinical validation, dose optimization, and early-phase human trials for the most advanced candidates, particularly asparaginase isoforms and alginate lyases. They also stress that bioprospecting must proceed under the Nagoya Protocol and ocean conservation frameworks to ensure that the exploitation of these genetic resources protects the very biodiversity that produced them. With antimicrobial resistance projected to claim tens of millions of lives by mid-century and inflammatory and oncological disease burdens rising worldwide, the humble enzymes of ocean microbes, refined by eons of evolutionary pressure in Earth’s most hostile environments, may prove to be among the most valuable biomedical resources humanity has yet to fully harvest.

Subject of Research: Marine microbial enzymes as therapeutic agents against chronic inflammation, cancer, and antimicrobial resistance

Article Title: Marine microbial enzymes as the next frontier in combating chronic inflammation, cancer, and global antimicrobial resistance

Article References: Kumar, A., Soratur, A., Kumar, S., Sarkar, A., Thiruchitrambalam, G., & Venmathi Maran, B. A. (2026). Marine microbial enzymes as the next frontier in combating chronic inflammation, cancer, and global antimicrobial resistance. Discover Oceans, 3(1), Article 49. https://doi.org/10.1007/s44289-026-00161-1

Image Credits: AI Generated

DOI: 10.1007/s44289-026-00161-1

Keywords: marine microbial enzymes, extremozymes, antimicrobial resistance, chronic inflammation, superoxide dismutase, L-asparaginase, alginate lyase, biofilm disruption, cancer therapy, marine biotechnology, NF-kB signaling, bioprospecting

Primary intramuscular lymphoma, meaning lymphoma that arises in or overwhelmingly involves skeletal muscle rather than lymph nodes or organs, is exceptionally rare across species. In humans, it accounts for less than 1.5 percent of extranodal lymphoma cases, with diffuse large B-cell lymphoma the most common form reported in muscle. Patients typically present with limb swelling, muscle pain, and rapidly worsening symptoms, and tumors have been described in muscles ranging from the sartorius and psoas to the gastrocnemius and soleus. In dogs, the literature is even thinner. Prior to this report, the authors could identify only eight cases of lymphoma with muscular involvement, and two of those lacked a definitive diagnosis. Strikingly, five of the confirmed canine cases were T-cell lymphomas, whereas B-cell disease dominates in human intramuscular cases, hinting at a genuine species difference in the biology of this rare tumor.

The Colorado State patient’s clinical course began deceptively. At the wellness visit, the focal tarsal edema was attributed to a soft tissue injury, and an ulcerated skin lesion on the right lateral neck yielded non-diagnostic cytology. Within hours, the dog was at an emergency clinic, where a 4 by 6 centimeter mass was found in the right inguinal region. Blood work, a chemistry profile, and a tick-borne disease panel were unremarkable. Three days later, diarrhea developed, the inguinal mass had grown to 7 centimeters, and the dog was started on metronidazole and anti-inflammatory prednisone. When he arrived at the oncology service, his right pelvic limb and inguinal region were severely edematous, the mass itself hidden beneath the swelling, and his peripheral lymph nodes were normal in size and texture, an important clue that this was not ordinary nodal lymphoma.

Computed tomography of the limb, abdomen, and thorax revealed the true extent of the disease. Multifocal, isoattenuating masses that enhanced strongly with contrast were scattered diffusely throughout the musculature of the body, involving the semimembranosus, adductor magnus, vastus lateralis, gluteal, gracilis, biceps femoris, epaxial, subscapularis, infraspinatus, and triceps muscles, with individual lesions ranging from 1 to 12 centimeters. Additional small masses sat near the caudal vena cava and adjacent to the ventricular free walls of the heart, though these were deemed too risky to sample. Angiography ruled out a thrombus as the cause of the edema. Ultrasound-guided fine needle aspirates of the thigh masses showed a population of individualized round cells with vacuolated cytoplasm and mild to moderate atypia, suggestive of a discrete cell neoplasm but not definitive. The differential list spanned lymphoma, embryonal rhabdomyosarcoma, extraosseous osteosarcoma, histiocytic sarcoma, and hemangiosarcoma.

Facing rapidly progressive edema, the team biopsied the left thigh masses with tru-cut needles and, before histopathology returned, began empirical chemotherapy with L-asparaginase and doxorubicin, chosen to cover both lymphoma and sarcoma differentials. The response was dramatic: the owners reported improvement within 24 hours and near-complete resolution of the edema within 72 hours. Histopathology, however, was perplexing. Sheets of neoplastic round cells infiltrated between myocytes, frequently isolating individual muscle fibers, with 25 mitoses counted in just two high-powered fields. Immunohistochemistry deepened the mystery. The cells were negative for CD3, CD20, Pax5, Desmin, CD204, and Iba1, but diffusely positive for vimentin, and roughly 75 percent showed strong nuclear reactivity for Mum-1, a marker typically associated with plasma cell tumors and certain B-cell lymphomas.

The decisive tool was PARR, the polymerase chain reaction assay for antigen receptor rearrangements, which detects clonal immune cell populations by examining gene rearrangements. The assay revealed polyclonal immunoglobulin genes but a clonal T-cell receptor arrangement, directly contradicting the plasma cell tumor interpretation suggested by the Mum-1 staining. Additional immunohistochemistry for CD34 and CD30 came back negative, excluding myeloid neoplasms and anaplastic large cell lymphoma, both of which can express Mum-1. The final diagnosis was T-cell lymphoma with aberrant Mum-1 expression and loss of the pan-T-cell marker CD3. Aberrant Mum-1 expression has been described before in canine and feline T-cell lymphoma, and loss of CD3 occurs in roughly 22.8 percent of canine T-cell lymphomas assessed by flow cytometry, but the combination made this case diagnostically treacherous. In total, achieving a definitive diagnosis took 31 days from the first chemotherapy dose.

Treatment continued with single-agent doxorubicin every three weeks, but eleven days after the third dose the disease declared its aggression. A new 5.8 by 5.2 centimeter fixed mass appeared at the base of the left ear with facial swelling, concerning for progression and possible central nervous system involvement, while peripheral lymph nodes remained unaffected. Cytology confirmed the same neoplastic population. The protocol was switched to a combination of lomustine and L-asparaginase, and within two days the facial mass had nearly resolved, only to recur and progress within eight days, eventually surrounding the left eye. A palliative single 6 Gy fraction of radiation therapy was delivered to the left side of the head, followed by one cycle of an MVPP protocol combining mechlorethamine, vinblastine, procarbazine, and prednisolone. Radiation rapidly reduced the facial swelling, and the report notes this is the only documented use of radiation therapy for intramuscular lymphoma in a dog.

The reprieve was brief. One week after radiation and MVPP, the facial swelling had improved and ventral edema was stable, but eleven days later edema progressed along the limbs and ventrum, and for the first time the dog had trouble rising and appeared uncomfortable. His owners elected humane euthanasia 63 days after initial presentation. No necropsy was performed, leaving open the question of whether the intramuscular masses represented a true primary muscular lymphoma or systemic spread, though the authors argue the overwhelming muscle burden, mild lymphadenomegaly, and complete absence of peripheral lymphadenopathy or organomegaly throughout the course favor a primary muscular process. Even at 63 days, the survival represents one of the longest reported for an dog with an aggressive lymphoma and significant intramuscular involvement.

The case carries several lessons for veterinary oncology, and echoes for comparative medicine. Intramuscular lymphoma should be on the differential list for any animal presenting with acutely progressive limb edema and multifocal muscle masses, even when lymph nodes are normal. Diagnosis demands a multimodal arsenal: contrast-enhanced CT to map disease extent, cytology and histopathology to characterize the cells, immunohistochemistry to define the lineage, and PARR or flow cytometry to resolve clonality when marker expression is misleading. The authors acknowledge that, in hindsight, a multiagent protocol such as CHOP, or an alkylator-rich LOPP regimen given the T-cell phenotype, would likely have been the preferred first-line approach had the diagnosis been known earlier. Instead, the urgency of the edema forced empirical monotherapy before the diagnosis was secure, a common dilemma with this tumor type.

Ultimately, the report underscores both the promise and the limits of modern veterinary cancer care. This tumor responded, at least transiently, to L-asparaginase, doxorubicin, lomustine with L-asparaginase, MVPP chemotherapy, and focal radiation, yet every response was measured in days to weeks, and the prognosis remains guarded. With fewer than ten documented canine cases and only a scattering of human reports, no consensus exists on optimal diagnosis or treatment, and each carefully documented case materially expands the field. The Colorado State team hopes that complete reporting of future cases, including imaging, immunophenotyping, clonality testing, and outcomes, will eventually yield a shared framework for this rare and relentless disease, one that in dogs appears to favor T-cells, strike through muscle, and progress faster than clinicians can comfortably respond.

Subject of Research: A rare canine T-cell lymphoma with extensive intramuscular involvement and aberrant Mum-1 expression

Article Title: T-cell lymphoma with significant intramuscular involvement with Mum-1 expression in a dog

Article References: Gutwillig, M., Schaffer, P., Yoon, P., & Vickery, K. (2026). T-cell lymphoma with significant intramuscular involvement with Mum-1 expression in a dog. Veterinary Oncology, 3(1), Article 21. https://doi.org/10.1186/s44356-026-00075-2

Image Credits: AI Generated

DOI: 10.1186/s44356-026-00075-2

Keywords: canine lymphoma, T-cell lymphoma, intramuscular lymphoma, Mum-1, veterinary oncology, immunohistochemistry, PARR, doxorubicin, L-asparaginase, radiation therapy, computed tomography, extranodal lymphoma